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2 Subunit Vaccines against MERS-CoVa.\nName Functionality and antigenicity Adjuvant Route Animal models Antibody response Cellular immune response Protective efficacy References\nSubunit vaccines based on MERS-CoV full-length S protein\nMERS S-2P protein Binds to DPP4 receptor and MERS-CoV S-NTD, RBD, and S2-specific neutralizing mAbs (G2, D12, and G4, respectively) SAS I.M. BALB/c mice Elicits neutralizing Abs in mice, neutralizing 7 pseudotyped MERS-CoV N/A N/A Pallesen et al., 2017\nSubunit vaccines based on MERS-CoV RBD protein\nrRBD (S367-606) protein N/A Alum Hydro + CpG or poly(I:C); IFA + CpG (mouse); Alum (NHPs) I.M. or S.C. BALB/c mice; NHPs Elicits MERS-CoV RBD-specific Abs in mice (IgG, IgG1, IgG2a, and IgG2b) and NHPs (IgG), neutralizing pseudotyped (mouse: \u003c 1:5 × 102) and live (NHPs: \u003c 1:5 × 102) MERS-CoV (EMC2012 strain) Induces MERS-CoV RBD-specific cellular immune responses (IFN-γ, TNF-α, IL-2, IL-4, IL-6, and IL-10) in mice and/or monkeys Partially protects vaccinated NHPs from challenge of MERS-CoV (EMC2012 strain, 6.5 × 107 TCID50) with alleviated pneumonia and decreased viral load Lan et al., 2014, 2015\nRBD (S377-662)-Fc protein Binds to DPP4 receptor Poly(I:C); Montanide I.N. or S.C. BALB/c mice Elicits MERS-CoV S1- and RBD-specific Abs (IgA, IgG (\u003e 1:104), IgG1, IgG2a, and IgG3) in mice, neutralizing (≥ 1:2.4 × 102) live MERS-CoV (EMC2012 strain) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice N/A Du et al., 2013c; Ma et al., 2014b\nRBD (S377-588)-Fc protein Binds to DPP4 receptor and MERS-CoV RBD specific neutralizing mAbs (Mersmab1, m336, m337, and m338) Montanide; MF59; AddaVax I.M. or S.C. BALB/c mice; hDPP4-Tg mice; Rabbits Elicits MERS-CoV S1 and RBD-specific Abs in mice (IgG (\u003e 1:105), IgG1, and IgG2a) and rabbits (IgG), neutralizing 17 pseudotyped (≥ 1:104) and 2 live (≥ 1:103) MERS-CoV (EMC2012 and London1-2012 strains) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice Protects vaccinated Ad5/hDPP4-transduced BALB/c mice and majority (4/6) of vaccinated hDPP4-Tg mice from MERS-CoV (EMC2012 strain, 105 PFU for BALB/c; 103–4 TCID50 for Tg) challenge, without immunological toxicity or eosinophilic immune enhancement Du et al., 2013a; Ma et al., 2014b; Tang et al., 2015; Zhang et al., 2016; Nyon et al., 2018\nRBD-Fd protein Binds to DPP4 receptor and MERS-CoV RBD-specific neutralizing mAbs (Mersmab1, m336, m337, and m338) MF59; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits MERS-CoV S1-specific Abs (IgG (\u003e 1:105), IgG1, and IgG2a) in mice, neutralizing at least 9 pseudotyped (\u003e 1:104) and live (\u003e 1:103) MERS-CoV (EMC2012 strain) N/A Protects majority (5/6) of vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Tai et al., 2016\nRBD (T579N) protein Binds to receptor DPP4 and MERS-CoV RBD-specific neutralizing mAbs (hMS-1, m336, m337, and m338) Montanide; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits neutralizing Abs (\u003e 1:3 × 103) in mice against live MERS-CoV (EMC2012 strain) N/A Protects all vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Du et al., 2016a\nSubunit vaccines based on non-RBD MERS-CoV S protein fragments\nS1 protein N/A Ribi; Alum pho I.M. BALB/c mice; NHPs Elicits MERS-CoV S1-specific Abs in mice (IgG and IgG1) and NHPs (IgG), neutralizing 8 pseudotyped and live MERS-CoV (JordanN3 strain) N/A Protects vaccinated NHPs from challenge of MERS-CoV (JordanN3 strain, 5 × 106 PFU) with reduced abnormalities on chest CT Wang et al., 2015\nS1 protein N/A Advax + SAS I.M. Dromedary camels; Alpacas Elicits neutralizing Abs in dromedary camels (≥ 1:80) and alpacas (≥ 1:6.4 × 102) against live MERS-CoV (EMC2012 strain) N/A Protects vaccinated dromedary camels and alpacas from challenge of MERS-CoV (EMC2012 strain, 107 TCID50) with reduced and delayed viral shedding in the upper airways (in camels) or complete protection (in alpacas) Adney et al., 2019\nrNTD protein N/A Alum pho + CpG I.M. BALB/c mice; Ad5-hDPP4 mice Elicits MERS-CoV S-NTD-specific Abs (IgG, ≥ 1:104) in mice, neutralizing pseudotyped and live (1:40) MERS-CoV (EMC2012 strain) Induces MERS-CoV S-NTD-specific cellular immune responses (IFN-γ, IL-2, IL-6, IL-10, and IL-17A) in mice Protects vaccinated Ad5-hDPP4-transduced mice from challenge of MERS-CoV (EMC2012 strain, 105 PFU) with reduced lung abnormalities and respiratory tract pathology Jiaming et al., 2017\nSP3 peptide (aa736-761) N/A Freund’s N/A BALB/c mice; NZW rabbits Elicits MERS-CoV S-specific Abs (IgG, 1:104) in rabbits, neutralizing pseudotyped MERS-CoV N/A N/A Yang et al., 2014a\naaa, amino acid; Abs, antibodies; Ad5, adenovirus serotype 5; Ad5-hDPP4 mice, Ad5-hDPP4-transuced mice; Alum hydro, aluminum hydroxide; Alum pho, Aluminum phosphate; hDPP4, human dipeptidyl peptidase 4; hDPP4-Tg mice, transgenic mice expressing MERS-CoV receptor human DPP4; IFA, incomplete Freund’s adjuvant; I.M., intramuscular; I.N., intranasal; mAbs, monoclonal antibodies; Montanide, Montanide ISA51; N/A, not reported; NHPs, non-human primates; NZW, rabbits, New Zealand White rabbits; PFU, plaque-forming unit; rRBD, recombinant RBD; SAS, Sigma Adjuvant System; S.C., subcutaneous; TCID50, median tissue culture infectious dose; TNF-α, tumor necrosis factor (TNF)-alpha."}

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2 Subunit Vaccines against MERS-CoVa.\nName Functionality and antigenicity Adjuvant Route Animal models Antibody response Cellular immune response Protective efficacy References\nSubunit vaccines based on MERS-CoV full-length S protein\nMERS S-2P protein Binds to DPP4 receptor and MERS-CoV S-NTD, RBD, and S2-specific neutralizing mAbs (G2, D12, and G4, respectively) SAS I.M. BALB/c mice Elicits neutralizing Abs in mice, neutralizing 7 pseudotyped MERS-CoV N/A N/A Pallesen et al., 2017\nSubunit vaccines based on MERS-CoV RBD protein\nrRBD (S367-606) protein N/A Alum Hydro + CpG or poly(I:C); IFA + CpG (mouse); Alum (NHPs) I.M. or S.C. BALB/c mice; NHPs Elicits MERS-CoV RBD-specific Abs in mice (IgG, IgG1, IgG2a, and IgG2b) and NHPs (IgG), neutralizing pseudotyped (mouse: \u003c 1:5 × 102) and live (NHPs: \u003c 1:5 × 102) MERS-CoV (EMC2012 strain) Induces MERS-CoV RBD-specific cellular immune responses (IFN-γ, TNF-α, IL-2, IL-4, IL-6, and IL-10) in mice and/or monkeys Partially protects vaccinated NHPs from challenge of MERS-CoV (EMC2012 strain, 6.5 × 107 TCID50) with alleviated pneumonia and decreased viral load Lan et al., 2014, 2015\nRBD (S377-662)-Fc protein Binds to DPP4 receptor Poly(I:C); Montanide I.N. or S.C. BALB/c mice Elicits MERS-CoV S1- and RBD-specific Abs (IgA, IgG (\u003e 1:104), IgG1, IgG2a, and IgG3) in mice, neutralizing (≥ 1:2.4 × 102) live MERS-CoV (EMC2012 strain) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice N/A Du et al., 2013c; Ma et al., 2014b\nRBD (S377-588)-Fc protein Binds to DPP4 receptor and MERS-CoV RBD specific neutralizing mAbs (Mersmab1, m336, m337, and m338) Montanide; MF59; AddaVax I.M. or S.C. BALB/c mice; hDPP4-Tg mice; Rabbits Elicits MERS-CoV S1 and RBD-specific Abs in mice (IgG (\u003e 1:105), IgG1, and IgG2a) and rabbits (IgG), neutralizing 17 pseudotyped (≥ 1:104) and 2 live (≥ 1:103) MERS-CoV (EMC2012 and London1-2012 strains) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice Protects vaccinated Ad5/hDPP4-transduced BALB/c mice and majority (4/6) of vaccinated hDPP4-Tg mice from MERS-CoV (EMC2012 strain, 105 PFU for BALB/c; 103–4 TCID50 for Tg) challenge, without immunological toxicity or eosinophilic immune enhancement Du et al., 2013a; Ma et al., 2014b; Tang et al., 2015; Zhang et al., 2016; Nyon et al., 2018\nRBD-Fd protein Binds to DPP4 receptor and MERS-CoV RBD-specific neutralizing mAbs (Mersmab1, m336, m337, and m338) MF59; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits MERS-CoV S1-specific Abs (IgG (\u003e 1:105), IgG1, and IgG2a) in mice, neutralizing at least 9 pseudotyped (\u003e 1:104) and live (\u003e 1:103) MERS-CoV (EMC2012 strain) N/A Protects majority (5/6) of vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Tai et al., 2016\nRBD (T579N) protein Binds to receptor DPP4 and MERS-CoV RBD-specific neutralizing mAbs (hMS-1, m336, m337, and m338) Montanide; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits neutralizing Abs (\u003e 1:3 × 103) in mice against live MERS-CoV (EMC2012 strain) N/A Protects all vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Du et al., 2016a\nSubunit vaccines based on non-RBD MERS-CoV S protein fragments\nS1 protein N/A Ribi; Alum pho I.M. BALB/c mice; NHPs Elicits MERS-CoV S1-specific Abs in mice (IgG and IgG1) and NHPs (IgG), neutralizing 8 pseudotyped and live MERS-CoV (JordanN3 strain) N/A Protects vaccinated NHPs from challenge of MERS-CoV (JordanN3 strain, 5 × 106 PFU) with reduced abnormalities on chest CT Wang et al., 2015\nS1 protein N/A Advax + SAS I.M. Dromedary camels; Alpacas Elicits neutralizing Abs in dromedary camels (≥ 1:80) and alpacas (≥ 1:6.4 × 102) against live MERS-CoV (EMC2012 strain) N/A Protects vaccinated dromedary camels and alpacas from challenge of MERS-CoV (EMC2012 strain, 107 TCID50) with reduced and delayed viral shedding in the upper airways (in camels) or complete protection (in alpacas) Adney et al., 2019\nrNTD protein N/A Alum pho + CpG I.M. BALB/c mice; Ad5-hDPP4 mice Elicits MERS-CoV S-NTD-specific Abs (IgG, ≥ 1:104) in mice, neutralizing pseudotyped and live (1:40) MERS-CoV (EMC2012 strain) Induces MERS-CoV S-NTD-specific cellular immune responses (IFN-γ, IL-2, IL-6, IL-10, and IL-17A) in mice Protects vaccinated Ad5-hDPP4-transduced mice from challenge of MERS-CoV (EMC2012 strain, 105 PFU) with reduced lung abnormalities and respiratory tract pathology Jiaming et al., 2017\nSP3 peptide (aa736-761) N/A Freund’s N/A BALB/c mice; NZW rabbits Elicits MERS-CoV S-specific Abs (IgG, 1:104) in rabbits, neutralizing pseudotyped MERS-CoV N/A N/A Yang et al., 2014a\naaa, amino acid; Abs, antibodies; Ad5, adenovirus serotype 5; Ad5-hDPP4 mice, Ad5-hDPP4-transuced mice; Alum hydro, aluminum hydroxide; Alum pho, Aluminum phosphate; hDPP4, human dipeptidyl peptidase 4; hDPP4-Tg mice, transgenic mice expressing MERS-CoV receptor human DPP4; IFA, incomplete Freund’s adjuvant; I.M., intramuscular; I.N., intranasal; mAbs, monoclonal antibodies; Montanide, Montanide ISA51; N/A, not reported; NHPs, non-human primates; NZW, rabbits, New Zealand White rabbits; PFU, plaque-forming unit; rRBD, recombinant RBD; SAS, Sigma Adjuvant System; S.C., subcutaneous; TCID50, median tissue culture infectious dose; TNF-α, tumor necrosis factor (TNF)-alpha."}

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T14","span":{"begin":3606,"end":3611},"obj":"Body_part"},{"id":"T15","span":{"begin":4474,"end":4478},"obj":"Body_part"},{"id":"T16","span":{"begin":4497,"end":4514},"obj":"Body_part"},{"id":"T17","span":{"begin":5343,"end":5349},"obj":"Body_part"}],"attributes":[{"id":"A14","pred":"uberon_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/UBERON_0001443"},{"id":"A15","pred":"uberon_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A16","pred":"uberon_id","subj":"T16","obj":"http://purl.obolibrary.org/obo/UBERON_0000065"},{"id":"A17","pred":"uberon_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/UBERON_0000479"}],"text":"TABLE 2 Subunit Vaccines against MERS-CoVa.\nName Functionality and antigenicity Adjuvant Route Animal models Antibody response Cellular immune response Protective efficacy References\nSubunit vaccines based on MERS-CoV full-length S protein\nMERS S-2P protein Binds to DPP4 receptor and MERS-CoV S-NTD, RBD, and S2-specific neutralizing mAbs (G2, D12, and G4, respectively) SAS I.M. BALB/c mice Elicits neutralizing Abs in mice, neutralizing 7 pseudotyped MERS-CoV N/A N/A Pallesen et al., 2017\nSubunit vaccines based on MERS-CoV RBD protein\nrRBD (S367-606) protein N/A Alum Hydro + CpG or poly(I:C); IFA + CpG (mouse); Alum (NHPs) I.M. or S.C. BALB/c mice; NHPs Elicits MERS-CoV RBD-specific Abs in mice (IgG, IgG1, IgG2a, and IgG2b) and NHPs (IgG), neutralizing pseudotyped (mouse: \u003c 1:5 × 102) and live (NHPs: \u003c 1:5 × 102) MERS-CoV (EMC2012 strain) Induces MERS-CoV RBD-specific cellular immune responses (IFN-γ, TNF-α, IL-2, IL-4, IL-6, and IL-10) in mice and/or monkeys Partially protects vaccinated NHPs from challenge of MERS-CoV (EMC2012 strain, 6.5 × 107 TCID50) with alleviated pneumonia and decreased viral load Lan et al., 2014, 2015\nRBD (S377-662)-Fc protein Binds to DPP4 receptor Poly(I:C); Montanide I.N. or S.C. BALB/c mice Elicits MERS-CoV S1- and RBD-specific Abs (IgA, IgG (\u003e 1:104), IgG1, IgG2a, and IgG3) in mice, neutralizing (≥ 1:2.4 × 102) live MERS-CoV (EMC2012 strain) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice N/A Du et al., 2013c; Ma et al., 2014b\nRBD (S377-588)-Fc protein Binds to DPP4 receptor and MERS-CoV RBD specific neutralizing mAbs (Mersmab1, m336, m337, and m338) Montanide; MF59; AddaVax I.M. or S.C. BALB/c mice; hDPP4-Tg mice; Rabbits Elicits MERS-CoV S1 and RBD-specific Abs in mice (IgG (\u003e 1:105), IgG1, and IgG2a) and rabbits (IgG), neutralizing 17 pseudotyped (≥ 1:104) and 2 live (≥ 1:103) MERS-CoV (EMC2012 and London1-2012 strains) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice Protects vaccinated Ad5/hDPP4-transduced BALB/c mice and majority (4/6) of vaccinated hDPP4-Tg mice from MERS-CoV (EMC2012 strain, 105 PFU for BALB/c; 103–4 TCID50 for Tg) challenge, without immunological toxicity or eosinophilic immune enhancement Du et al., 2013a; Ma et al., 2014b; Tang et al., 2015; Zhang et al., 2016; Nyon et al., 2018\nRBD-Fd protein Binds to DPP4 receptor and MERS-CoV RBD-specific neutralizing mAbs (Mersmab1, m336, m337, and m338) MF59; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits MERS-CoV S1-specific Abs (IgG (\u003e 1:105), IgG1, and IgG2a) in mice, neutralizing at least 9 pseudotyped (\u003e 1:104) and live (\u003e 1:103) MERS-CoV (EMC2012 strain) N/A Protects majority (5/6) of vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Tai et al., 2016\nRBD (T579N) protein Binds to receptor DPP4 and MERS-CoV RBD-specific neutralizing mAbs (hMS-1, m336, m337, and m338) Montanide; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits neutralizing Abs (\u003e 1:3 × 103) in mice against live MERS-CoV (EMC2012 strain) N/A Protects all vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Du et al., 2016a\nSubunit vaccines based on non-RBD MERS-CoV S protein fragments\nS1 protein N/A Ribi; Alum pho I.M. BALB/c mice; NHPs Elicits MERS-CoV S1-specific Abs in mice (IgG and IgG1) and NHPs (IgG), neutralizing 8 pseudotyped and live MERS-CoV (JordanN3 strain) N/A Protects vaccinated NHPs from challenge of MERS-CoV (JordanN3 strain, 5 × 106 PFU) with reduced abnormalities on chest CT Wang et al., 2015\nS1 protein N/A Advax + SAS I.M. Dromedary camels; Alpacas Elicits neutralizing Abs in dromedary camels (≥ 1:80) and alpacas (≥ 1:6.4 × 102) against live MERS-CoV (EMC2012 strain) N/A Protects vaccinated dromedary camels and alpacas from challenge of MERS-CoV (EMC2012 strain, 107 TCID50) with reduced and delayed viral shedding in the upper airways (in camels) or complete protection (in alpacas) Adney et al., 2019\nrNTD protein N/A Alum pho + CpG I.M. BALB/c mice; Ad5-hDPP4 mice Elicits MERS-CoV S-NTD-specific Abs (IgG, ≥ 1:104) in mice, neutralizing pseudotyped and live (1:40) MERS-CoV (EMC2012 strain) Induces MERS-CoV S-NTD-specific cellular immune responses (IFN-γ, IL-2, IL-6, IL-10, and IL-17A) in mice Protects vaccinated Ad5-hDPP4-transduced mice from challenge of MERS-CoV (EMC2012 strain, 105 PFU) with reduced lung abnormalities and respiratory tract pathology Jiaming et al., 2017\nSP3 peptide (aa736-761) N/A Freund’s N/A BALB/c mice; NZW rabbits Elicits MERS-CoV S-specific Abs (IgG, 1:104) in rabbits, neutralizing pseudotyped MERS-CoV N/A N/A Yang et al., 2014a\naaa, amino acid; Abs, antibodies; Ad5, adenovirus serotype 5; Ad5-hDPP4 mice, Ad5-hDPP4-transuced mice; Alum hydro, aluminum hydroxide; Alum pho, Aluminum phosphate; hDPP4, human dipeptidyl peptidase 4; hDPP4-Tg mice, transgenic mice expressing MERS-CoV receptor human DPP4; IFA, incomplete Freund’s adjuvant; I.M., intramuscular; I.N., intranasal; mAbs, monoclonal antibodies; Montanide, Montanide ISA51; N/A, not reported; NHPs, non-human primates; NZW, rabbits, New Zealand White rabbits; PFU, plaque-forming unit; rRBD, recombinant RBD; SAS, Sigma Adjuvant System; S.C., subcutaneous; TCID50, median tissue culture infectious dose; TNF-α, tumor necrosis factor (TNF)-alpha."}

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T232","span":{"begin":306,"end":309},"obj":"Disease"},{"id":"T234","span":{"begin":1110,"end":1119},"obj":"Disease"},{"id":"T235","span":{"begin":2057,"end":2060},"obj":"Disease"},{"id":"T236","span":{"begin":2384,"end":2386},"obj":"Disease"},{"id":"T237","span":{"begin":4112,"end":4115},"obj":"Disease"},{"id":"T238","span":{"begin":4147,"end":4150},"obj":"Disease"},{"id":"T240","span":{"begin":4275,"end":4278},"obj":"Disease"},{"id":"T242","span":{"begin":4382,"end":4385},"obj":"Disease"},{"id":"T243","span":{"begin":4773,"end":4776},"obj":"Disease"},{"id":"T244","span":{"begin":4801,"end":4804},"obj":"Disease"},{"id":"T245","span":{"begin":4817,"end":4820},"obj":"Disease"},{"id":"T246","span":{"begin":5358,"end":5368},"obj":"Disease"},{"id":"T247","span":{"begin":5382,"end":5387},"obj":"Disease"}],"attributes":[{"id":"A232","pred":"mondo_id","subj":"T232","obj":"http://purl.obolibrary.org/obo/MONDO_0008449"},{"id":"A233","pred":"mondo_id","subj":"T232","obj":"http://purl.obolibrary.org/obo/MONDO_0018075"},{"id":"A234","pred":"mondo_id","subj":"T234","obj":"http://purl.obolibrary.org/obo/MONDO_0005249"},{"id":"A235","pred":"mondo_id","subj":"T235","obj":"http://purl.obolibrary.org/obo/MONDO_0011194"},{"id":"A236","pred":"mondo_id","subj":"T236","obj":"http://purl.obolibrary.org/obo/MONDO_0010526"},{"id":"A237","pred":"mondo_id","subj":"T237","obj":"http://purl.obolibrary.org/obo/MONDO_0011194"},{"id":"A238","pred":"mondo_id","subj":"T238","obj":"http://purl.obolibrary.org/obo/MONDO_0008449"},{"id":"A239","pred":"mondo_id","subj":"T238","obj":"http://purl.obolibrary.org/obo/MONDO_0018075"},{"id":"A240","pred":"mondo_id","subj":"T240","obj":"http://purl.obolibrary.org/obo/MONDO_0008449"},{"id":"A241","pred":"mondo_id","subj":"T240","obj":"http://purl.obolibrary.org/obo/MONDO_0018075"},{"id":"A242","pred":"mondo_id","subj":"T242","obj":"http://purl.obolibrary.org/obo/MONDO_0011194"},{"id":"A243","pred":"mondo_id","subj":"T243","obj":"http://purl.obolibrary.org/obo/MONDO_0011194"},{"id":"A244","pred":"mondo_id","subj":"T244","obj":"http://purl.obolibrary.org/obo/MONDO_0011194"},{"id":"A245","pred":"mondo_id","subj":"T245","obj":"http://purl.obolibrary.org/obo/MONDO_0011194"},{"id":"A246","pred":"mondo_id","subj":"T246","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A247","pred":"mondo_id","subj":"T247","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"}],"text":"TABLE 2 Subunit Vaccines against MERS-CoVa.\nName Functionality and antigenicity Adjuvant Route Animal models Antibody response Cellular immune response Protective efficacy References\nSubunit vaccines based on MERS-CoV full-length S protein\nMERS S-2P protein Binds to DPP4 receptor and MERS-CoV S-NTD, RBD, and S2-specific neutralizing mAbs (G2, D12, and G4, respectively) SAS I.M. BALB/c mice Elicits neutralizing Abs in mice, neutralizing 7 pseudotyped MERS-CoV N/A N/A Pallesen et al., 2017\nSubunit vaccines based on MERS-CoV RBD protein\nrRBD (S367-606) protein N/A Alum Hydro + CpG or poly(I:C); IFA + CpG (mouse); Alum (NHPs) I.M. or S.C. BALB/c mice; NHPs Elicits MERS-CoV RBD-specific Abs in mice (IgG, IgG1, IgG2a, and IgG2b) and NHPs (IgG), neutralizing pseudotyped (mouse: \u003c 1:5 × 102) and live (NHPs: \u003c 1:5 × 102) MERS-CoV (EMC2012 strain) Induces MERS-CoV RBD-specific cellular immune responses (IFN-γ, TNF-α, IL-2, IL-4, IL-6, and IL-10) in mice and/or monkeys Partially protects vaccinated NHPs from challenge of MERS-CoV (EMC2012 strain, 6.5 × 107 TCID50) with alleviated pneumonia and decreased viral load Lan et al., 2014, 2015\nRBD (S377-662)-Fc protein Binds to DPP4 receptor Poly(I:C); Montanide I.N. or S.C. BALB/c mice Elicits MERS-CoV S1- and RBD-specific Abs (IgA, IgG (\u003e 1:104), IgG1, IgG2a, and IgG3) in mice, neutralizing (≥ 1:2.4 × 102) live MERS-CoV (EMC2012 strain) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice N/A Du et al., 2013c; Ma et al., 2014b\nRBD (S377-588)-Fc protein Binds to DPP4 receptor and MERS-CoV RBD specific neutralizing mAbs (Mersmab1, m336, m337, and m338) Montanide; MF59; AddaVax I.M. or S.C. BALB/c mice; hDPP4-Tg mice; Rabbits Elicits MERS-CoV S1 and RBD-specific Abs in mice (IgG (\u003e 1:105), IgG1, and IgG2a) and rabbits (IgG), neutralizing 17 pseudotyped (≥ 1:104) and 2 live (≥ 1:103) MERS-CoV (EMC2012 and London1-2012 strains) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice Protects vaccinated Ad5/hDPP4-transduced BALB/c mice and majority (4/6) of vaccinated hDPP4-Tg mice from MERS-CoV (EMC2012 strain, 105 PFU for BALB/c; 103–4 TCID50 for Tg) challenge, without immunological toxicity or eosinophilic immune enhancement Du et al., 2013a; Ma et al., 2014b; Tang et al., 2015; Zhang et al., 2016; Nyon et al., 2018\nRBD-Fd protein Binds to DPP4 receptor and MERS-CoV RBD-specific neutralizing mAbs (Mersmab1, m336, m337, and m338) MF59; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits MERS-CoV S1-specific Abs (IgG (\u003e 1:105), IgG1, and IgG2a) in mice, neutralizing at least 9 pseudotyped (\u003e 1:104) and live (\u003e 1:103) MERS-CoV (EMC2012 strain) N/A Protects majority (5/6) of vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Tai et al., 2016\nRBD (T579N) protein Binds to receptor DPP4 and MERS-CoV RBD-specific neutralizing mAbs (hMS-1, m336, m337, and m338) Montanide; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits neutralizing Abs (\u003e 1:3 × 103) in mice against live MERS-CoV (EMC2012 strain) N/A Protects all vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Du et al., 2016a\nSubunit vaccines based on non-RBD MERS-CoV S protein fragments\nS1 protein N/A Ribi; Alum pho I.M. BALB/c mice; NHPs Elicits MERS-CoV S1-specific Abs in mice (IgG and IgG1) and NHPs (IgG), neutralizing 8 pseudotyped and live MERS-CoV (JordanN3 strain) N/A Protects vaccinated NHPs from challenge of MERS-CoV (JordanN3 strain, 5 × 106 PFU) with reduced abnormalities on chest CT Wang et al., 2015\nS1 protein N/A Advax + SAS I.M. Dromedary camels; Alpacas Elicits neutralizing Abs in dromedary camels (≥ 1:80) and alpacas (≥ 1:6.4 × 102) against live MERS-CoV (EMC2012 strain) N/A Protects vaccinated dromedary camels and alpacas from challenge of MERS-CoV (EMC2012 strain, 107 TCID50) with reduced and delayed viral shedding in the upper airways (in camels) or complete protection (in alpacas) Adney et al., 2019\nrNTD protein N/A Alum pho + CpG I.M. BALB/c mice; Ad5-hDPP4 mice Elicits MERS-CoV S-NTD-specific Abs (IgG, ≥ 1:104) in mice, neutralizing pseudotyped and live (1:40) MERS-CoV (EMC2012 strain) Induces MERS-CoV S-NTD-specific cellular immune responses (IFN-γ, IL-2, IL-6, IL-10, and IL-17A) in mice Protects vaccinated Ad5-hDPP4-transduced mice from challenge of MERS-CoV (EMC2012 strain, 105 PFU) with reduced lung abnormalities and respiratory tract pathology Jiaming et al., 2017\nSP3 peptide (aa736-761) N/A Freund’s N/A BALB/c mice; NZW rabbits Elicits MERS-CoV S-specific Abs (IgG, 1:104) in rabbits, neutralizing pseudotyped MERS-CoV N/A N/A Yang et al., 2014a\naaa, amino acid; Abs, antibodies; Ad5, adenovirus serotype 5; Ad5-hDPP4 mice, Ad5-hDPP4-transuced mice; Alum hydro, aluminum hydroxide; Alum pho, Aluminum phosphate; hDPP4, human dipeptidyl peptidase 4; hDPP4-Tg mice, transgenic mice expressing MERS-CoV receptor human DPP4; IFA, incomplete Freund’s adjuvant; I.M., intramuscular; I.N., intranasal; mAbs, monoclonal antibodies; Montanide, Montanide ISA51; N/A, not reported; NHPs, non-human primates; NZW, rabbits, New Zealand White rabbits; PFU, plaque-forming unit; rRBD, recombinant RBD; SAS, Sigma Adjuvant System; S.C., subcutaneous; TCID50, median tissue culture infectious dose; TNF-α, tumor necrosis factor (TNF)-alpha."}

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T532","span":{"begin":100,"end":106},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_33208"},{"id":"T533","span":{"begin":320,"end":322},"obj":"http://purl.obolibrary.org/obo/CLO_0008922"},{"id":"T534","span":{"begin":320,"end":322},"obj":"http://purl.obolibrary.org/obo/CLO_0050052"},{"id":"T535","span":{"begin":351,"end":353},"obj":"http://purl.obolibrary.org/obo/CLO_0003414"},{"id":"T536","span":{"begin":383,"end":386},"obj":"http://purl.obolibrary.org/obo/CLO_0051568"},{"id":"T537","span":{"begin":480,"end":481},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T538","span":{"begin":485,"end":486},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T539","span":{"begin":584,"end":585},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T540","span":{"begin":629,"end":634},"obj":"http://purl.obolibrary.org/obo/CLO_0007836"},{"id":"T541","span":{"begin":797,"end":802},"obj":"http://purl.obolibrary.org/obo/CLO_0007836"},{"id":"T542","span":{"begin":812,"end":815},"obj":"http://purl.obolibrary.org/obo/CLO_0054060"},{"id":"T543","span":{"begin":841,"end":844},"obj":"http://purl.obolibrary.org/obo/CLO_0054060"},{"id":"T544","span":{"begin":944,"end":948},"obj":"http://purl.obolibrary.org/obo/PR_000001379"},{"id":"T545","span":{"begin":988,"end":995},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9479"},{"id":"T546","span":{"begin":1184,"end":1186},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"},{"id":"T547","span":{"begin":1286,"end":1288},"obj":"http://purl.obolibrary.org/obo/CLO_0050050"},{"id":"T548","span":{"begin":1388,"end":1391},"obj":"http://purl.obolibrary.org/obo/CLO_0054060"},{"id":"T549","span":{"begin":1442,"end":1444},"obj":"http://purl.obolibrary.org/obo/CLO_0050050"},{"id":"T550","span":{"begin":1491,"end":1495},"obj":"http://purl.obolibrary.org/obo/PR_000001379"},{"id":"T551","span":{"begin":1508,"end":1509},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T552","span":{"begin":1561,"end":1563},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"},{"id":"T553","span":{"begin":1768,"end":1770},"obj":"http://purl.obolibrary.org/obo/CLO_0050050"},{"id":"T554","span":{"begin":1808,"end":1813},"obj":"http://purl.obolibrary.org/obo/CLO_0001040"},{"id":"T555","span":{"begin":1973,"end":1975},"obj":"http://purl.obolibrary.org/obo/CLO_0050050"},{"id":"T556","span":{"begin":2022,"end":2026},"obj":"http://purl.obolibrary.org/obo/PR_000001379"},{"id":"T557","span":{"begin":2375,"end":2379},"obj":"http://purl.obolibrary.org/obo/CLO_0001185"},{"id":"T558","span":{"begin":2568,"end":2570},"obj":"http://purl.obolibrary.org/obo/CLO_0050050"},{"id":"T559","span":{"begin":2592,"end":2597},"obj":"http://purl.obolibrary.org/obo/CLO_0001040"},{"id":"T560","span":{"begin":2720,"end":2721},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T561","span":{"begin":3116,"end":3117},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T562","span":{"begin":3294,"end":3296},"obj":"http://purl.obolibrary.org/obo/CLO_0050050"},{"id":"T563","span":{"begin":3308,"end":3309},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T564","span":{"begin":3369,"end":3371},"obj":"http://purl.obolibrary.org/obo/CLO_0050050"},{"id":"T565","span":{"begin":3490,"end":3491},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T566","span":{"begin":3606,"end":3611},"obj":"http://www.ebi.ac.uk/efo/EFO_0000965"},{"id":"T567","span":{"begin":3634,"end":3636},"obj":"http://purl.obolibrary.org/obo/CLO_0050050"},{"id":"T568","span":{"begin":3648,"end":3649},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T569","span":{"begin":3659,"end":3662},"obj":"http://purl.obolibrary.org/obo/CLO_0051568"},{"id":"T570","span":{"begin":3680,"end":3686},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9837"},{"id":"T571","span":{"begin":3735,"end":3741},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9837"},{"id":"T572","span":{"begin":3774,"end":3777},"obj":"http://purl.obolibrary.org/obo/CLO_0054060"},{"id":"T573","span":{"begin":3821,"end":3822},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T574","span":{"begin":3854,"end":3860},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9837"},{"id":"T575","span":{"begin":3982,"end":3989},"obj":"http://purl.obolibrary.org/obo/UBERON_0001005"},{"id":"T576","span":{"begin":3994,"end":4000},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9837"},{"id":"T577","span":{"begin":4074,"end":4075},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T578","span":{"begin":4322,"end":4326},"obj":"http://purl.obolibrary.org/obo/PR_000001379"},{"id":"T579","span":{"begin":4474,"end":4478},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T580","span":{"begin":4474,"end":4478},"obj":"http://www.ebi.ac.uk/efo/EFO_0000934"},{"id":"T581","span":{"begin":4551,"end":4558},"obj":"http://purl.obolibrary.org/obo/PR_000018263"},{"id":"T582","span":{"begin":4574,"end":4575},"obj":"http://purl.o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2 Subunit Vaccines against MERS-CoVa.\nName Functionality and antigenicity Adjuvant Route Animal models Antibody response Cellular immune response Protective efficacy References\nSubunit vaccines based on MERS-CoV full-length S protein\nMERS S-2P protein Binds to DPP4 receptor and MERS-CoV S-NTD, RBD, and S2-specific neutralizing mAbs (G2, D12, and G4, respectively) SAS I.M. BALB/c mice Elicits neutralizing Abs in mice, neutralizing 7 pseudotyped MERS-CoV N/A N/A Pallesen et al., 2017\nSubunit vaccines based on MERS-CoV RBD protein\nrRBD (S367-606) protein N/A Alum Hydro + CpG or poly(I:C); IFA + CpG (mouse); Alum (NHPs) I.M. or S.C. BALB/c mice; NHPs Elicits MERS-CoV RBD-specific Abs in mice (IgG, IgG1, IgG2a, and IgG2b) and NHPs (IgG), neutralizing pseudotyped (mouse: \u003c 1:5 × 102) and live (NHPs: \u003c 1:5 × 102) MERS-CoV (EMC2012 strain) Induces MERS-CoV RBD-specific cellular immune responses (IFN-γ, TNF-α, IL-2, IL-4, IL-6, and IL-10) in mice and/or monkeys Partially protects vaccinated NHPs from challenge of MERS-CoV (EMC2012 strain, 6.5 × 107 TCID50) with alleviated pneumonia and decreased viral load Lan et al., 2014, 2015\nRBD (S377-662)-Fc protein Binds to DPP4 receptor Poly(I:C); Montanide I.N. or S.C. BALB/c mice Elicits MERS-CoV S1- and RBD-specific Abs (IgA, IgG (\u003e 1:104), IgG1, IgG2a, and IgG3) in mice, neutralizing (≥ 1:2.4 × 102) live MERS-CoV (EMC2012 strain) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice N/A Du et al., 2013c; Ma et al., 2014b\nRBD (S377-588)-Fc protein Binds to DPP4 receptor and MERS-CoV RBD specific neutralizing mAbs (Mersmab1, m336, m337, and m338) Montanide; MF59; AddaVax I.M. or S.C. BALB/c mice; hDPP4-Tg mice; Rabbits Elicits MERS-CoV S1 and RBD-specific Abs in mice (IgG (\u003e 1:105), IgG1, and IgG2a) and rabbits (IgG), neutralizing 17 pseudotyped (≥ 1:104) and 2 live (≥ 1:103) MERS-CoV (EMC2012 and London1-2012 strains) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice Protects vaccinated Ad5/hDPP4-transduced BALB/c mice and majority (4/6) of vaccinated hDPP4-Tg mice from MERS-CoV (EMC2012 strain, 105 PFU for BALB/c; 103–4 TCID50 for Tg) challenge, without immunological toxicity or eosinophilic immune enhancement Du et al., 2013a; Ma et al., 2014b; Tang et al., 2015; Zhang et al., 2016; Nyon et al., 2018\nRBD-Fd protein Binds to DPP4 receptor and MERS-CoV RBD-specific neutralizing mAbs (Mersmab1, m336, m337, and m338) MF59; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits MERS-CoV S1-specific Abs (IgG (\u003e 1:105), IgG1, and IgG2a) in mice, neutralizing at least 9 pseudotyped (\u003e 1:104) and live (\u003e 1:103) MERS-CoV (EMC2012 strain) N/A Protects majority (5/6) of vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Tai et al., 2016\nRBD (T579N) protein Binds to receptor DPP4 and MERS-CoV RBD-specific neutralizing mAbs (hMS-1, m336, m337, and m338) Montanide; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits neutralizing Abs (\u003e 1:3 × 103) in mice against live MERS-CoV (EMC2012 strain) N/A Protects all vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Du et al., 2016a\nSubunit vaccines based on non-RBD MERS-CoV S protein fragments\nS1 protein N/A Ribi; Alum pho I.M. BALB/c mice; NHPs Elicits MERS-CoV S1-specific Abs in mice (IgG and IgG1) and NHPs (IgG), neutralizing 8 pseudotyped and live MERS-CoV (JordanN3 strain) N/A Protects vaccinated NHPs from challenge of MERS-CoV (JordanN3 strain, 5 × 106 PFU) with reduced abnormalities on chest CT Wang et al., 2015\nS1 protein N/A Advax + SAS I.M. Dromedary camels; Alpacas Elicits neutralizing Abs in dromedary camels (≥ 1:80) and alpacas (≥ 1:6.4 × 102) against live MERS-CoV (EMC2012 strain) N/A Protects vaccinated dromedary camels and alpacas from challenge of MERS-CoV (EMC2012 strain, 107 TCID50) with reduced and delayed viral shedding in the upper airways (in camels) or complete protection (in alpacas) Adney et al., 2019\nrNTD protein N/A Alum pho + CpG I.M. BALB/c mice; Ad5-hDPP4 mice Elicits MERS-CoV S-NTD-specific Abs (IgG, ≥ 1:104) in mice, neutralizing pseudotyped and live (1:40) MERS-CoV (EMC2012 strain) Induces MERS-CoV S-NTD-specific cellular immune responses (IFN-γ, IL-2, IL-6, IL-10, and IL-17A) in mice Protects vaccinated Ad5-hDPP4-transduced mice from challenge of MERS-CoV (EMC2012 strain, 105 PFU) with reduced lung abnormalities and respiratory tract pathology Jiaming et al., 2017\nSP3 peptide (aa736-761) N/A Freund’s N/A BALB/c mice; NZW rabbits Elicits MERS-CoV S-specific Abs (IgG, 1:104) in rabbits, neutralizing pseudotyped MERS-CoV N/A N/A Yang et al., 2014a\naaa, amino acid; Abs, antibodies; Ad5, adenovirus serotype 5; Ad5-hDPP4 mice, Ad5-hDPP4-transuced mice; Alum hydro, aluminum hydroxide; Alum pho, Aluminum phosphate; hDPP4, human dipeptidyl peptidase 4; hDPP4-Tg mice, transgenic mice expressing MERS-CoV receptor human DPP4; IFA, incomplete Freund’s adjuvant; I.M., intramuscular; I.N., intranasal; mAbs, monoclonal antibodies; Montanide, Montanide ISA51; N/A, not reported; NHPs, non-human primates; NZW, rabbits, New Zealand White rabbits; PFU, plaque-forming unit; rRBD, recombinant RBD; SAS, Sigma Adjuvant System; S.C., subcutaneous; TCID50, median tissue culture infectious dose; TNF-α, tumor necrosis factor (TNF)-alpha."}

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2 Subunit Vaccines against MERS-CoVa.\nName Functionality and antigenicity Adjuvant Route Animal models Antibody response Cellular immune response Protective efficacy References\nSubunit vaccines based on MERS-CoV full-length S protein\nMERS S-2P protein Binds to DPP4 receptor and MERS-CoV S-NTD, RBD, and S2-specific neutralizing mAbs (G2, D12, and G4, respectively) SAS I.M. BALB/c mice Elicits neutralizing Abs in mice, neutralizing 7 pseudotyped MERS-CoV N/A N/A Pallesen et al., 2017\nSubunit vaccines based on MERS-CoV RBD protein\nrRBD (S367-606) protein N/A Alum Hydro + CpG or poly(I:C); IFA + CpG (mouse); Alum (NHPs) I.M. or S.C. BALB/c mice; NHPs Elicits MERS-CoV RBD-specific Abs in mice (IgG, IgG1, IgG2a, and IgG2b) and NHPs (IgG), neutralizing pseudotyped (mouse: \u003c 1:5 × 102) and live (NHPs: \u003c 1:5 × 102) MERS-CoV (EMC2012 strain) Induces MERS-CoV RBD-specific cellular immune responses (IFN-γ, TNF-α, IL-2, IL-4, IL-6, and IL-10) in mice and/or monkeys Partially protects vaccinated NHPs from challenge of MERS-CoV (EMC2012 strain, 6.5 × 107 TCID50) with alleviated pneumonia and decreased viral load Lan et al., 2014, 2015\nRBD (S377-662)-Fc protein Binds to DPP4 receptor Poly(I:C); Montanide I.N. or S.C. BALB/c mice Elicits MERS-CoV S1- and RBD-specific Abs (IgA, IgG (\u003e 1:104), IgG1, IgG2a, and IgG3) in mice, neutralizing (≥ 1:2.4 × 102) live MERS-CoV (EMC2012 strain) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice N/A Du et al., 2013c; Ma et al., 2014b\nRBD (S377-588)-Fc protein Binds to DPP4 receptor and MERS-CoV RBD specific neutralizing mAbs (Mersmab1, m336, m337, and m338) Montanide; MF59; AddaVax I.M. or S.C. BALB/c mice; hDPP4-Tg mice; Rabbits Elicits MERS-CoV S1 and RBD-specific Abs in mice (IgG (\u003e 1:105), IgG1, and IgG2a) and rabbits (IgG), neutralizing 17 pseudotyped (≥ 1:104) and 2 live (≥ 1:103) MERS-CoV (EMC2012 and London1-2012 strains) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice Protects vaccinated Ad5/hDPP4-transduced BALB/c mice and majority (4/6) of vaccinated hDPP4-Tg mice from MERS-CoV (EMC2012 strain, 105 PFU for BALB/c; 103–4 TCID50 for Tg) challenge, without immunological toxicity or eosinophilic immune enhancement Du et al., 2013a; Ma et al., 2014b; Tang et al., 2015; Zhang et al., 2016; Nyon et al., 2018\nRBD-Fd protein Binds to DPP4 receptor and MERS-CoV RBD-specific neutralizing mAbs (Mersmab1, m336, m337, and m338) MF59; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits MERS-CoV S1-specific Abs (IgG (\u003e 1:105), IgG1, and IgG2a) in mice, neutralizing at least 9 pseudotyped (\u003e 1:104) and live (\u003e 1:103) MERS-CoV (EMC2012 strain) N/A Protects majority (5/6) of vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Tai et al., 2016\nRBD (T579N) protein Binds to receptor DPP4 and MERS-CoV RBD-specific neutralizing mAbs (hMS-1, m336, m337, and m338) Montanide; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits neutralizing Abs (\u003e 1:3 × 103) in mice against live MERS-CoV (EMC2012 strain) N/A Protects all vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Du et al., 2016a\nSubunit vaccines based on non-RBD MERS-CoV S protein fragments\nS1 protein N/A Ribi; Alum pho I.M. BALB/c mice; NHPs Elicits MERS-CoV S1-specific Abs in mice (IgG and IgG1) and NHPs (IgG), neutralizing 8 pseudotyped and live MERS-CoV (JordanN3 strain) N/A Protects vaccinated NHPs from challenge of MERS-CoV (JordanN3 strain, 5 × 106 PFU) with reduced abnormalities on chest CT Wang et al., 2015\nS1 protein N/A Advax + SAS I.M. Dromedary camels; Alpacas Elicits neutralizing Abs in dromedary camels (≥ 1:80) and alpacas (≥ 1:6.4 × 102) against live MERS-CoV (EMC2012 strain) N/A Protects vaccinated dromedary camels and alpacas from challenge of MERS-CoV (EMC2012 strain, 107 TCID50) with reduced and delayed viral shedding in the upper airways (in camels) or complete protection (in alpacas) Adney et al., 2019\nrNTD protein N/A Alum pho + CpG I.M. BALB/c mice; Ad5-hDPP4 mice Elicits MERS-CoV S-NTD-specific Abs (IgG, ≥ 1:104) in mice, neutralizing pseudotyped and live (1:40) MERS-CoV (EMC2012 strain) Induces MERS-CoV S-NTD-specific cellular immune responses (IFN-γ, IL-2, IL-6, IL-10, and IL-17A) in mice Protects vaccinated Ad5-hDPP4-transduced mice from challenge of MERS-CoV (EMC2012 strain, 105 PFU) with reduced lung abnormalities and respiratory tract pathology Jiaming et al., 2017\nSP3 peptide (aa736-761) N/A Freund’s N/A BALB/c mice; NZW rabbits Elicits MERS-CoV S-specific Abs (IgG, 1:104) in rabbits, neutralizing pseudotyped MERS-CoV N/A N/A Yang et al., 2014a\naaa, amino acid; Abs, antibodies; Ad5, adenovirus serotype 5; Ad5-hDPP4 mice, Ad5-hDPP4-transuced mice; Alum hydro, aluminum hydroxide; Alum pho, Aluminum phosphate; hDPP4, human dipeptidyl peptidase 4; hDPP4-Tg mice, transgenic mice expressing MERS-CoV receptor human DPP4; IFA, incomplete Freund’s adjuvant; I.M., intramuscular; I.N., intranasal; mAbs, monoclonal antibodies; Montanide, Montanide ISA51; N/A, not reported; NHPs, non-human primates; NZW, rabbits, New Zealand White rabbits; PFU, plaque-forming unit; rRBD, recombinant RBD; SAS, Sigma Adjuvant System; S.C., subcutaneous; TCID50, median tissue culture infectious dose; TNF-α, tumor necrosis factor (TNF)-alpha."}

{"project":"LitCovid-PD-HP","denotations":[{"id":"T12","span":{"begin":1110,"end":1119},"obj":"Phenotype"},{"id":"T13","span":{"begin":5382,"end":5387},"obj":"Phenotype"}],"attributes":[{"id":"A12","pred":"hp_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A13","pred":"hp_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/HP_0002664"}],"text":"TABLE 2 Subunit Vaccines against MERS-CoVa.\nName Functionality and antigenicity Adjuvant Route Animal models Antibody response Cellular immune response Protective efficacy References\nSubunit vaccines based on MERS-CoV full-length S protein\nMERS S-2P protein Binds to DPP4 receptor and MERS-CoV S-NTD, RBD, and S2-specific neutralizing mAbs (G2, D12, and G4, respectively) SAS I.M. BALB/c mice Elicits neutralizing Abs in mice, neutralizing 7 pseudotyped MERS-CoV N/A N/A Pallesen et al., 2017\nSubunit vaccines based on MERS-CoV RBD protein\nrRBD (S367-606) protein N/A Alum Hydro + CpG or poly(I:C); IFA + CpG (mouse); Alum (NHPs) I.M. or S.C. BALB/c mice; NHPs Elicits MERS-CoV RBD-specific Abs in mice (IgG, IgG1, IgG2a, and IgG2b) and NHPs (IgG), neutralizing pseudotyped (mouse: \u003c 1:5 × 102) and live (NHPs: \u003c 1:5 × 102) MERS-CoV (EMC2012 strain) Induces MERS-CoV RBD-specific cellular immune responses (IFN-γ, TNF-α, IL-2, IL-4, IL-6, and IL-10) in mice and/or monkeys Partially protects vaccinated NHPs from challenge of MERS-CoV (EMC2012 strain, 6.5 × 107 TCID50) with alleviated pneumonia and decreased viral load Lan et al., 2014, 2015\nRBD (S377-662)-Fc protein Binds to DPP4 receptor Poly(I:C); Montanide I.N. or S.C. BALB/c mice Elicits MERS-CoV S1- and RBD-specific Abs (IgA, IgG (\u003e 1:104), IgG1, IgG2a, and IgG3) in mice, neutralizing (≥ 1:2.4 × 102) live MERS-CoV (EMC2012 strain) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice N/A Du et al., 2013c; Ma et al., 2014b\nRBD (S377-588)-Fc protein Binds to DPP4 receptor and MERS-CoV RBD specific neutralizing mAbs (Mersmab1, m336, m337, and m338) Montanide; MF59; AddaVax I.M. or S.C. BALB/c mice; hDPP4-Tg mice; Rabbits Elicits MERS-CoV S1 and RBD-specific Abs in mice (IgG (\u003e 1:105), IgG1, and IgG2a) and rabbits (IgG), neutralizing 17 pseudotyped (≥ 1:104) and 2 live (≥ 1:103) MERS-CoV (EMC2012 and London1-2012 strains) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice Protects vaccinated Ad5/hDPP4-transduced BALB/c mice and majority (4/6) of vaccinated hDPP4-Tg mice from MERS-CoV (EMC2012 strain, 105 PFU for BALB/c; 103–4 TCID50 for Tg) challenge, without immunological toxicity or eosinophilic immune enhancement Du et al., 2013a; Ma et al., 2014b; Tang et al., 2015; Zhang et al., 2016; Nyon et al., 2018\nRBD-Fd protein Binds to DPP4 receptor and MERS-CoV RBD-specific neutralizing mAbs (Mersmab1, m336, m337, and m338) MF59; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits MERS-CoV S1-specific Abs (IgG (\u003e 1:105), IgG1, and IgG2a) in mice, neutralizing at least 9 pseudotyped (\u003e 1:104) and live (\u003e 1:103) MERS-CoV (EMC2012 strain) N/A Protects majority (5/6) of vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Tai et al., 2016\nRBD (T579N) protein Binds to receptor DPP4 and MERS-CoV RBD-specific neutralizing mAbs (hMS-1, m336, m337, and m338) Montanide; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits neutralizing Abs (\u003e 1:3 × 103) in mice against live MERS-CoV (EMC2012 strain) N/A Protects all vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Du et al., 2016a\nSubunit vaccines based on non-RBD MERS-CoV S protein fragments\nS1 protein N/A Ribi; Alum pho I.M. BALB/c mice; NHPs Elicits MERS-CoV S1-specific Abs in mice (IgG and IgG1) and NHPs (IgG), neutralizing 8 pseudotyped and live MERS-CoV (JordanN3 strain) N/A Protects vaccinated NHPs from challenge of MERS-CoV (JordanN3 strain, 5 × 106 PFU) with reduced abnormalities on chest CT Wang et al., 2015\nS1 protein N/A Advax + SAS I.M. Dromedary camels; Alpacas Elicits neutralizing Abs in dromedary camels (≥ 1:80) and alpacas (≥ 1:6.4 × 102) against live MERS-CoV (EMC2012 strain) N/A Protects vaccinated dromedary camels and alpacas from challenge of MERS-CoV (EMC2012 strain, 107 TCID50) with reduced and delayed viral shedding in the upper airways (in camels) or complete protection (in alpacas) Adney et al., 2019\nrNTD protein N/A Alum pho + CpG I.M. BALB/c mice; Ad5-hDPP4 mice Elicits MERS-CoV S-NTD-specific Abs (IgG, ≥ 1:104) in mice, neutralizing pseudotyped and live (1:40) MERS-CoV (EMC2012 strain) Induces MERS-CoV S-NTD-specific cellular immune responses (IFN-γ, IL-2, IL-6, IL-10, and IL-17A) in mice Protects vaccinated Ad5-hDPP4-transduced mice from challenge of MERS-CoV (EMC2012 strain, 105 PFU) with reduced lung abnormalities and respiratory tract pathology Jiaming et al., 2017\nSP3 peptide (aa736-761) N/A Freund’s N/A BALB/c mice; NZW rabbits Elicits MERS-CoV S-specific Abs (IgG, 1:104) in rabbits, neutralizing pseudotyped MERS-CoV N/A N/A Yang et al., 2014a\naaa, amino acid; Abs, antibodies; Ad5, adenovirus serotype 5; Ad5-hDPP4 mice, Ad5-hDPP4-transuced mice; Alum hydro, aluminum hydroxide; Alum pho, Aluminum phosphate; hDPP4, human dipeptidyl peptidase 4; hDPP4-Tg mice, transgenic mice expressing MERS-CoV receptor human DPP4; IFA, incomplete Freund’s adjuvant; I.M., intramuscular; I.N., intranasal; mAbs, monoclonal antibodies; Montanide, Montanide ISA51; N/A, not reported; NHPs, non-human primates; NZW, rabbits, New Zealand White rabbits; PFU, plaque-forming unit; rRBD, recombinant RBD; SAS, Sigma Adjuvant System; S.C., subcutaneous; TCID50, median tissue culture infectious dose; TNF-α, tumor necrosis factor (TNF)-alpha."}

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T77","span":{"begin":134,"end":158},"obj":"http://purl.obolibrary.org/obo/GO_0002456"},{"id":"T78","span":{"begin":134,"end":158},"obj":"http://purl.obolibrary.org/obo/GO_0002449"},{"id":"T79","span":{"begin":134,"end":158},"obj":"http://purl.obolibrary.org/obo/GO_0002443"},{"id":"T80","span":{"begin":143,"end":158},"obj":"http://purl.obolibrary.org/obo/GO_0006955"},{"id":"T81","span":{"begin":903,"end":928},"obj":"http://purl.obolibrary.org/obo/GO_0002456"},{"id":"T82","span":{"begin":903,"end":928},"obj":"http://purl.obolibrary.org/obo/GO_0002449"},{"id":"T83","span":{"begin":903,"end":928},"obj":"http://purl.obolibrary.org/obo/GO_0002443"},{"id":"T84","span":{"begin":1454,"end":1479},"obj":"http://purl.obolibrary.org/obo/GO_0002456"},{"id":"T85","span":{"begin":1454,"end":1479},"obj":"http://purl.obolibrary.org/obo/GO_0002449"},{"id":"T86","span":{"begin":1454,"end":1479},"obj":"http://purl.obolibrary.org/obo/GO_0002443"},{"id":"T87","span":{"begin":1985,"end":2010},"obj":"http://purl.obolibrary.org/obo/GO_0002456"},{"id":"T88","span":{"begin":1985,"end":2010},"obj":"http://purl.obolibrary.org/obo/GO_0002449"},{"id":"T89","span":{"begin":1985,"end":2010},"obj":"http://purl.obolibrary.org/obo/GO_0002443"},{"id":"T90","span":{"begin":3954,"end":3968},"obj":"http://purl.obolibrary.org/obo/GO_0019076"},{"id":"T91","span":{"begin":4288,"end":4313},"obj":"http://purl.obolibrary.org/obo/GO_0002456"},{"id":"T92","span":{"begin":4288,"end":4313},"obj":"http://purl.obolibrary.org/obo/GO_0002449"},{"id":"T93","span":{"begin":4288,"end":4313},"obj":"http://purl.obolibrary.org/obo/GO_0002443"},{"id":"T94","span":{"begin":5388,"end":5396},"obj":"http://purl.obolibrary.org/obo/GO_0070265"},{"id":"T95","span":{"begin":5388,"end":5396},"obj":"http://purl.obolibrary.org/obo/GO_0019835"},{"id":"T96","span":{"begin":5388,"end":5396},"obj":"http://purl.obolibrary.org/obo/GO_0008219"},{"id":"T97","span":{"begin":5388,"end":5396},"obj":"http://purl.obolibrary.org/obo/GO_0001906"}],"text":"TABLE 2 Subunit Vaccines against MERS-CoVa.\nName Functionality and antigenicity Adjuvant Route Animal models Antibody response Cellular immune response Protective efficacy References\nSubunit vaccines based on MERS-CoV full-length S protein\nMERS S-2P protein Binds to DPP4 receptor and MERS-CoV S-NTD, RBD, and S2-specific neutralizing mAbs (G2, D12, and G4, respectively) SAS I.M. BALB/c mice Elicits neutralizing Abs in mice, neutralizing 7 pseudotyped MERS-CoV N/A N/A Pallesen et al., 2017\nSubunit vaccines based on MERS-CoV RBD protein\nrRBD (S367-606) protein N/A Alum Hydro + CpG or poly(I:C); IFA + CpG (mouse); Alum (NHPs) I.M. or S.C. BALB/c mice; NHPs Elicits MERS-CoV RBD-specific Abs in mice (IgG, IgG1, IgG2a, and IgG2b) and NHPs (IgG), neutralizing pseudotyped (mouse: \u003c 1:5 × 102) and live (NHPs: \u003c 1:5 × 102) MERS-CoV (EMC2012 strain) Induces MERS-CoV RBD-specific cellular immune responses (IFN-γ, TNF-α, IL-2, IL-4, IL-6, and IL-10) in mice and/or monkeys Partially protects vaccinated NHPs from challenge of MERS-CoV (EMC2012 strain, 6.5 × 107 TCID50) with alleviated pneumonia and decreased viral load Lan et al., 2014, 2015\nRBD (S377-662)-Fc protein Binds to DPP4 receptor Poly(I:C); Montanide I.N. or S.C. BALB/c mice Elicits MERS-CoV S1- and RBD-specific Abs (IgA, IgG (\u003e 1:104), IgG1, IgG2a, and IgG3) in mice, neutralizing (≥ 1:2.4 × 102) live MERS-CoV (EMC2012 strain) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice N/A Du et al., 2013c; Ma et al., 2014b\nRBD (S377-588)-Fc protein Binds to DPP4 receptor and MERS-CoV RBD specific neutralizing mAbs (Mersmab1, m336, m337, and m338) Montanide; MF59; AddaVax I.M. or S.C. BALB/c mice; hDPP4-Tg mice; Rabbits Elicits MERS-CoV S1 and RBD-specific Abs in mice (IgG (\u003e 1:105), IgG1, and IgG2a) and rabbits (IgG), neutralizing 17 pseudotyped (≥ 1:104) and 2 live (≥ 1:103) MERS-CoV (EMC2012 and London1-2012 strains) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice Protects vaccinated Ad5/hDPP4-transduced BALB/c mice and majority (4/6) of vaccinated hDPP4-Tg mice from MERS-CoV (EMC2012 strain, 105 PFU for BALB/c; 103–4 TCID50 for Tg) challenge, without immunological toxicity or eosinophilic immune enhancement Du et al., 2013a; Ma et al., 2014b; Tang et al., 2015; Zhang et al., 2016; Nyon et al., 2018\nRBD-Fd protein Binds to DPP4 receptor and MERS-CoV RBD-specific neutralizing mAbs (Mersmab1, m336, m337, and m338) MF59; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits MERS-CoV S1-specific Abs (IgG (\u003e 1:105), IgG1, and IgG2a) in mice, neutralizing at least 9 pseudotyped (\u003e 1:104) and live (\u003e 1:103) MERS-CoV (EMC2012 strain) N/A Protects majority (5/6) of vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Tai et al., 2016\nRBD (T579N) protein Binds to receptor DPP4 and MERS-CoV RBD-specific neutralizing mAbs (hMS-1, m336, m337, and m338) Montanide; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits neutralizing Abs (\u003e 1:3 × 103) in mice against live MERS-CoV (EMC2012 strain) N/A Protects all vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Du et al., 2016a\nSubunit vaccines based on non-RBD MERS-CoV S protein fragments\nS1 protein N/A Ribi; Alum pho I.M. BALB/c mice; NHPs Elicits MERS-CoV S1-specific Abs in mice (IgG and IgG1) and NHPs (IgG), neutralizing 8 pseudotyped and live MERS-CoV (JordanN3 strain) N/A Protects vaccinated NHPs from challenge of MERS-CoV (JordanN3 strain, 5 × 106 PFU) with reduced abnormalities on chest CT Wang et al., 2015\nS1 protein N/A Advax + SAS I.M. Dromedary camels; Alpacas Elicits neutralizing Abs in dromedary camels (≥ 1:80) and alpacas (≥ 1:6.4 × 102) against live MERS-CoV (EMC2012 strain) N/A Protects vaccinated dromedary camels and alpacas from challenge of MERS-CoV (EMC2012 strain, 107 TCID50) with reduced and delayed viral shedding in the upper airways (in camels) or complete protection (in alpacas) Adney et al., 2019\nrNTD protein N/A Alum pho + CpG I.M. BALB/c mice; Ad5-hDPP4 mice Elicits MERS-CoV S-NTD-specific Abs (IgG, ≥ 1:104) in mice, neutralizing pseudotyped and live (1:40) MERS-CoV (EMC2012 strain) Induces MERS-CoV S-NTD-specific cellular immune responses (IFN-γ, IL-2, IL-6, IL-10, and IL-17A) in mice Protects vaccinated Ad5-hDPP4-transduced mice from challenge of MERS-CoV (EMC2012 strain, 105 PFU) with reduced lung abnormalities and respiratory tract pathology Jiaming et al., 2017\nSP3 peptide (aa736-761) N/A Freund’s N/A BALB/c mice; NZW rabbits Elicits MERS-CoV S-specific Abs (IgG, 1:104) in rabbits, neutralizing pseudotyped MERS-CoV N/A N/A Yang et al., 2014a\naaa, amino acid; Abs, antibodies; Ad5, adenovirus serotype 5; Ad5-hDPP4 mice, Ad5-hDPP4-transuced mice; Alum hydro, aluminum hydroxide; Alum pho, Aluminum phosphate; hDPP4, human dipeptidyl peptidase 4; hDPP4-Tg mice, transgenic mice expressing MERS-CoV receptor human DPP4; IFA, incomplete Freund’s adjuvant; I.M., intramuscular; I.N., intranasal; mAbs, monoclonal antibodies; Montanide, Montanide ISA51; N/A, not reported; NHPs, non-human primates; NZW, rabbits, New Zealand White rabbits; PFU, plaque-forming unit; rRBD, recombinant RBD; SAS, Sigma Adjuvant System; S.C., subcutaneous; TCID50, median tissue culture infectious dose; TNF-α, tumor necrosis factor (TNF)-alpha."}

{"project":"2_test","denotations":[{"id":"32265848-28807998-36511173","span":{"begin":505,"end":509},"obj":"28807998"},{"id":"32265848-25405618-36511174","span":{"begin":1158,"end":1162},"obj":"25405618"},{"id":"32265848-26629538-36511175","span":{"begin":1164,"end":1168},"obj":"26629538"},{"id":"32265848-25874632-36511180","span":{"begin":2336,"end":2340},"obj":"25874632"},{"id":"32265848-25640653-36511181","span":{"begin":2356,"end":2360},"obj":"25640653"},{"id":"32265848-29496347-36511182","span":{"begin":2375,"end":2379},"obj":"29496347"},{"id":"32265848-27750111-36511183","span":{"begin":2844,"end":2848},"obj":"27750111"},{"id":"32265848-26218507-36511185","span":{"begin":3629,"end":3633},"obj":"26218507"},{"id":"32265848-30832356-36511186","span":{"begin":4053,"end":4057},"obj":"30832356"},{"id":"32265848-27899228-36511187","span":{"begin":4542,"end":4546},"obj":"27899228"}],"text":"TABLE 2 Subunit Vaccines against MERS-CoVa.\nName Functionality and antigenicity Adjuvant Route Animal models Antibody response Cellular immune response Protective efficacy References\nSubunit vaccines based on MERS-CoV full-length S protein\nMERS S-2P protein Binds to DPP4 receptor and MERS-CoV S-NTD, RBD, and S2-specific neutralizing mAbs (G2, D12, and G4, respectively) SAS I.M. BALB/c mice Elicits neutralizing Abs in mice, neutralizing 7 pseudotyped MERS-CoV N/A N/A Pallesen et al., 2017\nSubunit vaccines based on MERS-CoV RBD protein\nrRBD (S367-606) protein N/A Alum Hydro + CpG or poly(I:C); IFA + CpG (mouse); Alum (NHPs) I.M. or S.C. BALB/c mice; NHPs Elicits MERS-CoV RBD-specific Abs in mice (IgG, IgG1, IgG2a, and IgG2b) and NHPs (IgG), neutralizing pseudotyped (mouse: \u003c 1:5 × 102) and live (NHPs: \u003c 1:5 × 102) MERS-CoV (EMC2012 strain) Induces MERS-CoV RBD-specific cellular immune responses (IFN-γ, TNF-α, IL-2, IL-4, IL-6, and IL-10) in mice and/or monkeys Partially protects vaccinated NHPs from challenge of MERS-CoV (EMC2012 strain, 6.5 × 107 TCID50) with alleviated pneumonia and decreased viral load Lan et al., 2014, 2015\nRBD (S377-662)-Fc protein Binds to DPP4 receptor Poly(I:C); Montanide I.N. or S.C. BALB/c mice Elicits MERS-CoV S1- and RBD-specific Abs (IgA, IgG (\u003e 1:104), IgG1, IgG2a, and IgG3) in mice, neutralizing (≥ 1:2.4 × 102) live MERS-CoV (EMC2012 strain) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice N/A Du et al., 2013c; Ma et al., 2014b\nRBD (S377-588)-Fc protein Binds to DPP4 receptor and MERS-CoV RBD specific neutralizing mAbs (Mersmab1, m336, m337, and m338) Montanide; MF59; AddaVax I.M. or S.C. BALB/c mice; hDPP4-Tg mice; Rabbits Elicits MERS-CoV S1 and RBD-specific Abs in mice (IgG (\u003e 1:105), IgG1, and IgG2a) and rabbits (IgG), neutralizing 17 pseudotyped (≥ 1:104) and 2 live (≥ 1:103) MERS-CoV (EMC2012 and London1-2012 strains) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice Protects vaccinated Ad5/hDPP4-transduced BALB/c mice and majority (4/6) of vaccinated hDPP4-Tg mice from MERS-CoV (EMC2012 strain, 105 PFU for BALB/c; 103–4 TCID50 for Tg) challenge, without immunological toxicity or eosinophilic immune enhancement Du et al., 2013a; Ma et al., 2014b; Tang et al., 2015; Zhang et al., 2016; Nyon et al., 2018\nRBD-Fd protein Binds to DPP4 receptor and MERS-CoV RBD-specific neutralizing mAbs (Mersmab1, m336, m337, and m338) MF59; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits MERS-CoV S1-specific Abs (IgG (\u003e 1:105), IgG1, and IgG2a) in mice, neutralizing at least 9 pseudotyped (\u003e 1:104) and live (\u003e 1:103) MERS-CoV (EMC2012 strain) N/A Protects majority (5/6) of vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Tai et al., 2016\nRBD (T579N) protein Binds to receptor DPP4 and MERS-CoV RBD-specific neutralizing mAbs (hMS-1, m336, m337, and m338) Montanide; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits neutralizing Abs (\u003e 1:3 × 103) in mice against live MERS-CoV (EMC2012 strain) N/A Protects all vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Du et al., 2016a\nSubunit vaccines based on non-RBD MERS-CoV S protein fragments\nS1 protein N/A Ribi; Alum pho I.M. BALB/c mice; NHPs Elicits MERS-CoV S1-specific Abs in mice (IgG and IgG1) and NHPs (IgG), neutralizing 8 pseudotyped and live MERS-CoV (JordanN3 strain) N/A Protects vaccinated NHPs from challenge of MERS-CoV (JordanN3 strain, 5 × 106 PFU) with reduced abnormalities on chest CT Wang et al., 2015\nS1 protein N/A Advax + SAS I.M. Dromedary camels; Alpacas Elicits neutralizing Abs in dromedary camels (≥ 1:80) and alpacas (≥ 1:6.4 × 102) against live MERS-CoV (EMC2012 strain) N/A Protects vaccinated dromedary camels and alpacas from challenge of MERS-CoV (EMC2012 strain, 107 TCID50) with reduced and delayed viral shedding in the upper airways (in camels) or complete protection (in alpacas) Adney et al., 2019\nrNTD protein N/A Alum pho + CpG I.M. BALB/c mice; Ad5-hDPP4 mice Elicits MERS-CoV S-NTD-specific Abs (IgG, ≥ 1:104) in mice, neutralizing pseudotyped and live (1:40) MERS-CoV (EMC2012 strain) Induces MERS-CoV S-NTD-specific cellular immune responses (IFN-γ, IL-2, IL-6, IL-10, and IL-17A) in mice Protects vaccinated Ad5-hDPP4-transduced mice from challenge of MERS-CoV (EMC2012 strain, 105 PFU) with reduced lung abnormalities and respiratory tract pathology Jiaming et al., 2017\nSP3 peptide (aa736-761) N/A Freund’s N/A BALB/c mice; NZW rabbits Elicits MERS-CoV S-specific Abs (IgG, 1:104) in rabbits, neutralizing pseudotyped MERS-CoV N/A N/A Yang et al., 2014a\naaa, amino acid; Abs, antibodies; Ad5, adenovirus serotype 5; Ad5-hDPP4 mice, Ad5-hDPP4-transuced mice; Alum hydro, aluminum hydroxide; Alum pho, Aluminum phosphate; hDPP4, human dipeptidyl peptidase 4; hDPP4-Tg mice, transgenic mice expressing MERS-CoV receptor human DPP4; IFA, incomplete Freund’s adjuvant; I.M., intramuscular; I.N., intranasal; mAbs, monoclonal antibodies; Montanide, Montanide ISA51; N/A, not reported; NHPs, non-human primates; NZW, rabbits, New Zealand White rabbits; PFU, plaque-forming unit; rRBD, recombinant RBD; SAS, Sigma Adjuvant System; S.C., subcutaneous; TCID50, median tissue culture infectious dose; TNF-α, tumor necrosis factor (TNF)-alpha."}

{"project":"LitCovid-sentences","denotations":[{"id":"T235","span":{"begin":0,"end":44},"obj":"Sentence"},{"id":"T236","span":{"begin":45,"end":191},"obj":"Sentence"},{"id":"T237","span":{"begin":192,"end":248},"obj":"Sentence"},{"id":"T238","span":{"begin":249,"end":392},"obj":"Sentence"},{"id":"T239","span":{"begin":394,"end":509},"obj":"Sentence"},{"id":"T240","span":{"begin":510,"end":556},"obj":"Sentence"},{"id":"T241","span":{"begin":557,"end":662},"obj":"Sentence"},{"id":"T242","span":{"begin":664,"end":1168},"obj":"Sentence"},{"id":"T243","span":{"begin":1169,"end":1254},"obj":"Sentence"},{"id":"T244","span":{"begin":1256,"end":1545},"obj":"Sentence"},{"id":"T245","span":{"begin":1546,"end":1712},"obj":"Sentence"},{"id":"T246","span":{"begin":1714,"end":2379},"obj":"Sentence"},{"id":"T247","span":{"begin":2380,"end":2521},"obj":"Sentence"},{"id":"T248","span":{"begin":2523,"end":2848},"obj":"Sentence"},{"id":"T249","span":{"begin":2849,"end":2997},"obj":"Sentence"},{"id":"T250","span":{"begin":2999,"end":3230},"obj":"Sentence"},{"id":"T251","span":{"begin":3231,"end":3293},"obj":"Sentence"},{"id":"T252","span":{"begin":3294,"end":3331},"obj":"Sentence"},{"id":"T253","span":{"begin":3333,"end":3633},"obj":"Sentence"},{"id":"T254","span":{"begin":3634,"end":3668},"obj":"Sentence"},{"id":"T255","span":{"begin":3670,"end":4057},"obj":"Sentence"},{"id":"T256","span":{"begin":4058,"end":4097},"obj":"Sentence"},{"id":"T257","span":{"begin":4099,"end":4546},"obj":"Sentence"},{"id":"T258","span":{"begin":4547,"end":4738},"obj":"Sentence"},{"id":"T259","span":{"begin":4739,"end":5416},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"TABLE 2 Subunit Vaccines against MERS-CoVa.\nName Functionality and antigenicity Adjuvant Route Animal models Antibody response Cellular immune response Protective efficacy References\nSubunit vaccines based on MERS-CoV full-length S protein\nMERS S-2P protein Binds to DPP4 receptor and MERS-CoV S-NTD, RBD, and S2-specific neutralizing mAbs (G2, D12, and G4, respectively) SAS I.M. BALB/c mice Elicits neutralizing Abs in mice, neutralizing 7 pseudotyped MERS-CoV N/A N/A Pallesen et al., 2017\nSubunit vaccines based on MERS-CoV RBD protein\nrRBD (S367-606) protein N/A Alum Hydro + CpG or poly(I:C); IFA + CpG (mouse); Alum (NHPs) I.M. or S.C. BALB/c mice; NHPs Elicits MERS-CoV RBD-specific Abs in mice (IgG, IgG1, IgG2a, and IgG2b) and NHPs (IgG), neutralizing pseudotyped (mouse: \u003c 1:5 × 102) and live (NHPs: \u003c 1:5 × 102) MERS-CoV (EMC2012 strain) Induces MERS-CoV RBD-specific cellular immune responses (IFN-γ, TNF-α, IL-2, IL-4, IL-6, and IL-10) in mice and/or monkeys Partially protects vaccinated NHPs from challenge of MERS-CoV (EMC2012 strain, 6.5 × 107 TCID50) with alleviated pneumonia and decreased viral load Lan et al., 2014, 2015\nRBD (S377-662)-Fc protein Binds to DPP4 receptor Poly(I:C); Montanide I.N. or S.C. BALB/c mice Elicits MERS-CoV S1- and RBD-specific Abs (IgA, IgG (\u003e 1:104), IgG1, IgG2a, and IgG3) in mice, neutralizing (≥ 1:2.4 × 102) live MERS-CoV (EMC2012 strain) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice N/A Du et al., 2013c; Ma et al., 2014b\nRBD (S377-588)-Fc protein Binds to DPP4 receptor and MERS-CoV RBD specific neutralizing mAbs (Mersmab1, m336, m337, and m338) Montanide; MF59; AddaVax I.M. or S.C. BALB/c mice; hDPP4-Tg mice; Rabbits Elicits MERS-CoV S1 and RBD-specific Abs in mice (IgG (\u003e 1:105), IgG1, and IgG2a) and rabbits (IgG), neutralizing 17 pseudotyped (≥ 1:104) and 2 live (≥ 1:103) MERS-CoV (EMC2012 and London1-2012 strains) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice Protects vaccinated Ad5/hDPP4-transduced BALB/c mice and majority (4/6) of vaccinated hDPP4-Tg mice from MERS-CoV (EMC2012 strain, 105 PFU for BALB/c; 103–4 TCID50 for Tg) challenge, without immunological toxicity or eosinophilic immune enhancement Du et al., 2013a; Ma et al., 2014b; Tang et al., 2015; Zhang et al., 2016; Nyon et al., 2018\nRBD-Fd protein Binds to DPP4 receptor and MERS-CoV RBD-specific neutralizing mAbs (Mersmab1, m336, m337, and m338) MF59; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits MERS-CoV S1-specific Abs (IgG (\u003e 1:105), IgG1, and IgG2a) in mice, neutralizing at least 9 pseudotyped (\u003e 1:104) and live (\u003e 1:103) MERS-CoV (EMC2012 strain) N/A Protects majority (5/6) of vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Tai et al., 2016\nRBD (T579N) protein Binds to receptor DPP4 and MERS-CoV RBD-specific neutralizing mAbs (hMS-1, m336, m337, and m338) Montanide; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits neutralizing Abs (\u003e 1:3 × 103) in mice against live MERS-CoV (EMC2012 strain) N/A Protects all vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Du et al., 2016a\nSubunit vaccines based on non-RBD MERS-CoV S protein fragments\nS1 protein N/A Ribi; Alum pho I.M. BALB/c mice; NHPs Elicits MERS-CoV S1-specific Abs in mice (IgG and IgG1) and NHPs (IgG), neutralizing 8 pseudotyped and live MERS-CoV (JordanN3 strain) N/A Protects vaccinated NHPs from challenge of MERS-CoV (JordanN3 strain, 5 × 106 PFU) with reduced abnormalities on chest CT Wang et al., 2015\nS1 protein N/A Advax + SAS I.M. Dromedary camels; Alpacas Elicits neutralizing Abs in dromedary camels (≥ 1:80) and alpacas (≥ 1:6.4 × 102) against live MERS-CoV (EMC2012 strain) N/A Protects vaccinated dromedary camels and alpacas from challenge of MERS-CoV (EMC2012 strain, 107 TCID50) with reduced and delayed viral shedding in the upper airways (in camels) or complete protection (in alpacas) Adney et al., 2019\nrNTD protein N/A Alum pho + CpG I.M. BALB/c mice; Ad5-hDPP4 mice Elicits MERS-CoV S-NTD-specific Abs (IgG, ≥ 1:104) in mice, neutralizing pseudotyped and live (1:40) MERS-CoV (EMC2012 strain) Induces MERS-CoV S-NTD-specific cellular immune responses (IFN-γ, IL-2, IL-6, IL-10, and IL-17A) in mice Protects vaccinated Ad5-hDPP4-transduced mice from challenge of MERS-CoV (EMC2012 strain, 105 PFU) with reduced lung abnormalities and respiratory tract pathology Jiaming et al., 2017\nSP3 peptide (aa736-761) N/A Freund’s N/A BALB/c mice; NZW rabbits Elicits MERS-CoV S-specific Abs (IgG, 1:104) in rabbits, neutralizing pseudotyped MERS-CoV N/A N/A Yang et al., 2014a\naaa, amino acid; Abs, antibodies; Ad5, adenovirus serotype 5; Ad5-hDPP4 mice, Ad5-hDPP4-transuced mice; Alum hydro, aluminum hydroxide; Alum pho, Aluminum phosphate; hDPP4, human dipeptidyl peptidase 4; hDPP4-Tg mice, transgenic mice expressing MERS-CoV receptor human DPP4; IFA, incomplete Freund’s adjuvant; I.M., intramuscular; I.N., intranasal; mAbs, monoclonal antibodies; Montanide, Montanide ISA51; N/A, not reported; NHPs, non-human primates; NZW, rabbits, New Zealand White rabbits; PFU, plaque-forming unit; rRBD, recombinant RBD; SAS, Sigma Adjuvant System; S.C., subcutaneous; TCID50, median tissue culture infectious dose; TNF-α, tumor necrosis factor (TNF)-alpha."}

{"project":"LitCovid-PMC-OGER-BB","denotations":[{"id":"T733","span":{"begin":34,"end":38},"obj":"SP_9"},{"id":"T19177","span":{"begin":34,"end":38},"obj":"SP_9"}],"text":"TABLE 2 Subunit Vaccines against MERS-CoVa.\nName Functionality and antigenicity Adjuvant Route Animal models Antibody response Cellular immune response Protective efficacy References\nSubunit vaccines based on MERS-CoV full-length S protein\nMERS S-2P protein Binds to DPP4 receptor and MERS-CoV S-NTD, RBD, and S2-specific neutralizing mAbs (G2, D12, and G4, respectively) SAS I.M. BALB/c mice Elicits neutralizing Abs in mice, neutralizing 7 pseudotyped MERS-CoV N/A N/A Pallesen et al., 2017\nSubunit vaccines based on MERS-CoV RBD protein\nrRBD (S367-606) protein N/A Alum Hydro + CpG or poly(I:C); IFA + CpG (mouse); Alum (NHPs) I.M. or S.C. BALB/c mice; NHPs Elicits MERS-CoV RBD-specific Abs in mice (IgG, IgG1, IgG2a, and IgG2b) and NHPs (IgG), neutralizing pseudotyped (mouse: \u003c 1:5 × 102) and live (NHPs: \u003c 1:5 × 102) MERS-CoV (EMC2012 strain) Induces MERS-CoV RBD-specific cellular immune responses (IFN-γ, TNF-α, IL-2, IL-4, IL-6, and IL-10) in mice and/or monkeys Partially protects vaccinated NHPs from challenge of MERS-CoV (EMC2012 strain, 6.5 × 107 TCID50) with alleviated pneumonia and decreased viral load Lan et al., 2014, 2015\nRBD (S377-662)-Fc protein Binds to DPP4 receptor Poly(I:C); Montanide I.N. or S.C. BALB/c mice Elicits MERS-CoV S1- and RBD-specific Abs (IgA, IgG (\u003e 1:104), IgG1, IgG2a, and IgG3) in mice, neutralizing (≥ 1:2.4 × 102) live MERS-CoV (EMC2012 strain) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice N/A Du et al., 2013c; Ma et al., 2014b\nRBD (S377-588)-Fc protein Binds to DPP4 receptor and MERS-CoV RBD specific neutralizing mAbs (Mersmab1, m336, m337, and m338) Montanide; MF59; AddaVax I.M. or S.C. BALB/c mice; hDPP4-Tg mice; Rabbits Elicits MERS-CoV S1 and RBD-specific Abs in mice (IgG (\u003e 1:105), IgG1, and IgG2a) and rabbits (IgG), neutralizing 17 pseudotyped (≥ 1:104) and 2 live (≥ 1:103) MERS-CoV (EMC2012 and London1-2012 strains) Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice Protects vaccinated Ad5/hDPP4-transduced BALB/c mice and majority (4/6) of vaccinated hDPP4-Tg mice from MERS-CoV (EMC2012 strain, 105 PFU for BALB/c; 103–4 TCID50 for Tg) challenge, without immunological toxicity or eosinophilic immune enhancement Du et al., 2013a; Ma et al., 2014b; Tang et al., 2015; Zhang et al., 2016; Nyon et al., 2018\nRBD-Fd protein Binds to DPP4 receptor and MERS-CoV RBD-specific neutralizing mAbs (Mersmab1, m336, m337, and m338) MF59; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits MERS-CoV S1-specific Abs (IgG (\u003e 1:105), IgG1, and IgG2a) in mice, neutralizing at least 9 pseudotyped (\u003e 1:104) and live (\u003e 1:103) MERS-CoV (EMC2012 strain) N/A Protects majority (5/6) of vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Tai et al., 2016\nRBD (T579N) protein Binds to receptor DPP4 and MERS-CoV RBD-specific neutralizing mAbs (hMS-1, m336, m337, and m338) Montanide; Alum I.M. or S.C. BALB/c mice; hDPP4-Tg mice Elicits neutralizing Abs (\u003e 1:3 × 103) in mice against live MERS-CoV (EMC2012 strain) N/A Protects all vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50) Du et al., 2016a\nSubunit vaccines based on non-RBD MERS-CoV S protein fragments\nS1 protein N/A Ribi; Alum pho I.M. BALB/c mice; NHPs Elicits MERS-CoV S1-specific Abs in mice (IgG and IgG1) and NHPs (IgG), neutralizing 8 pseudotyped and live MERS-CoV (JordanN3 strain) N/A Protects vaccinated NHPs from challenge of MERS-CoV (JordanN3 strain, 5 × 106 PFU) with reduced abnormalities on chest CT Wang et al., 2015\nS1 protein N/A Advax + SAS I.M. Dromedary camels; Alpacas Elicits neutralizing Abs in dromedary camels (≥ 1:80) and alpacas (≥ 1:6.4 × 102) against live MERS-CoV (EMC2012 strain) N/A Protects vaccinated dromedary camels and alpacas from challenge of MERS-CoV (EMC2012 strain, 107 TCID50) with reduced and delayed viral shedding in the upper airways (in camels) or complete protection (in alpacas) Adney et al., 2019\nrNTD protein N/A Alum pho + CpG I.M. BALB/c mice; Ad5-hDPP4 mice Elicits MERS-CoV S-NTD-specific Abs (IgG, ≥ 1:104) in mice, neutralizing pseudotyped and live (1:40) MERS-CoV (EMC2012 strain) Induces MERS-CoV S-NTD-specific cellular immune responses (IFN-γ, IL-2, IL-6, IL-10, and IL-17A) in mice Protects vaccinated Ad5-hDPP4-transduced mice from challenge of MERS-CoV (EMC2012 strain, 105 PFU) with reduced lung abnormalities and respiratory tract pathology Jiaming et al., 2017\nSP3 peptide (aa736-761) N/A Freund’s N/A BALB/c mice; NZW rabbits Elicits MERS-CoV S-specific Abs (IgG, 1:104) in rabbits, neutralizing pseudotyped MERS-CoV N/A N/A Yang et al., 2014a\naaa, amino acid; Abs, antibodies; Ad5, adenovirus serotype 5; Ad5-hDPP4 mice, Ad5-hDPP4-transuced mice; Alum hydro, aluminum hydroxide; Alum pho, Aluminum phosphate; hDPP4, human dipeptidyl peptidase 4; hDPP4-Tg mice, transgenic mice expressing MERS-CoV receptor human DPP4; IFA, incomplete Freund’s adjuvant; I.M., intramuscular; I.N., intranasal; mAbs, monoclonal antibodies; Montanide, Montanide ISA51; N/A, not reported; NHPs, non-human primates; NZW, rabbits, New Zealand White rabbits; PFU, plaque-forming unit; rRBD, recombinant RBD; SAS, Sigma Adjuvant System; S.C., subcutaneous; TCID50, median tissue culture infectious dose; TNF-α, tumor necrosis factor (TNF)-alpha."}