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Id Subject Object Predicate Lexical cue
T1 0-61 Sentence denotes The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines
T2 63-254 Sentence denotes The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern.
T3 255-327 Sentence denotes However, no specific antiviral treatments or vaccines are available yet.
T4 328-444 Sentence denotes This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2.
T5 446-633 Sentence denotes An outbreak of 2019-novel coronavirus (SARS-CoV-2) that causes atypical pneumonia (COVID-19) has raged in China since mid-December 2019 and has spread to 26 countries (February 20, 2020).
T6 634-807 Sentence denotes The epidemic was identified by the first four cases confirmed on December 29, 2019 and was traced to the Huanan Seafood Wholesale Market, Wuhan city, Hubei Province, China1.
T7 808-948 Sentence denotes A total of 75,465 cases with SARS-CoV-2 infections have been confirmed up to date (February 20, 2020), and 2,236 people have died in China2.
T8 949-1158 Sentence denotes COVID-19 spreads rapidly by human-to-human transmission with a median incubation period of 3.0 days (range, 0 to 24.0), and the time from symptom onset to developing pneumonia is 4.0 days (range, 2.0 to 7.0)3.
T9 1159-1307 Sentence denotes Respiratory droplets and direct contact are conventional transmission routes for SARS-CoV-2, and fecal-to-oral transmission might also have a role3.
T10 1308-1380 Sentence denotes Fever, dry cough, and fatigue are common symptoms at onset of COVID-194.
T11 1381-1476 Sentence denotes Most patients have lymphopenia and bilateral ground-glass opacity changes on chest CT scans4,5.
T12 1477-1579 Sentence denotes No specific antiviral treatments or vaccines are available because it is a new emerging viral disease.
T13 1580-1642 Sentence denotes Development of SARS-CoV-2-based vaccines is urgently required.
T14 1643-1871 Sentence denotes The entire virus particle-based preparation of vaccines, including inactivated and attenuated virus vaccines is advisable, because it is based on previous studies about the prevention and control of seasonal influenza vaccines6.
T15 1872-2012 Sentence denotes The first SARS-CoV-2 (Wuhan-Hu-1) was successfully sequenced and its genomic sequence submitted to GenBank on January 5, 2020 (Accession no.
T16 2013-2026 Sentence denotes MN908947.3)7.
T17 2027-2269 Sentence denotes Subsequently large-scale culture of SARS-CoV-2 was quickly performed, and an inactivated virus vaccine could be prepared through the employment of established physical and chemical methods such as UV light, formaldehyde, and β-propiolactone8.
T18 2270-2579 Sentence denotes The development of attenuated-virus vaccines is also possible by carefully screening the serially propagated SARS-CoV-2 with reduced pathogenesis such as induced minimal lung injury, diminished limited neutrophil influx, and increased anti-inflammatory cytokine expressions compared with the wild-type virus9.
T19 2580-2683 Sentence denotes Both inactivated and attenuated virus vaccines have their own disadvantages and side effects (Table 1).
T20 2684-2814 Sentence denotes Alternatively, new vaccine designs based on the putative protective antigen/peptides derived from SARS-CoV-2 should be considered.
T21 2815-2884 Sentence denotes Table 1 Advantages and disadvantages of different vaccine strategies.
T22 2885-2937 Sentence denotes Vaccine strategy Advantages Disadvantages References
T23 2938-3091 Sentence denotes Inactivated virus vaccines Easy to prepare; safety; high-titer neutralizing antibodies Potential inappropriate for highly immunosuppressed individuals 25
T24 3092-3241 Sentence denotes Attenuated virus vaccines Rapid development; induce high immune responses Phenotypic or genotypic reversion possible; can still cause some disease 25
T25 3242-3455 Sentence denotes Subunit vaccines High safety; consistent production; can induce cellular and humoral immune responses; high-titer neutralizing antibodies High cost; lower immunogenicity; require repeated doses and adjuvants 12,14
T26 3456-3578 Sentence denotes Viral vector vaccines Safety; induces high cellular and humoral immune responses Possibly present pre-existing immunity 12
T27 3579-3728 Sentence denotes DNA vaccines Easier to design; high safety; high-titer neutralizing antibodies Lower immune responses in humans; repeated doses may cause toxicity 23
T28 3729-3870 Sentence denotes mRNA vaccines Easier to design; high degree of adaptability; induce strong immune responses Highly unstable under physiological conditions 23
T29 3871-4143 Sentence denotes Accumulated releases of SARS-CoV-2 genomes such as GenBank accession numbers MN908947.3, MN975262.1, NC_045512.2, MN997409.1, MN985325.1, MN988669.1, MN988668.1, MN994468.1, MN994467.1, MN988713.1, and MN938384.1 facilitate the development of virus-based subunit vaccines.
T30 4144-4478 Sentence denotes SARS-CoV-2, which is similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), is an enveloped, single- and positive-stranded RNA virus with a genome comprising 29,891 nucleotides, which encode the 12 putative open reading frames responsible for the synthesis of viral structural and nonstructural proteins7,10.
T31 4479-4599 Sentence denotes A mature SARS-CoV-2 has four structural proteins, namely, envelope (E), membrane (M), nucleocapsid (N), and spike (S)10.
T32 4600-4721 Sentence denotes All these proteins may serve as antigens to stimulate neutralizing antibodies and increase CD4+/CD8+ T-cell responses8,9.
T33 4722-4957 Sentence denotes However, subunit vaccines require multiple booster shots and suitable adjuvants to work, and certain subunit vaccines such as hepatitis B surface antigen, PreS1, and PreS2 may fail to yield protective response when tested clinically11.
T34 4958-5076 Sentence denotes The DNA and mRNA vaccines that are easier to design and proceed into clinical trials very quickly remain experimental.
T35 5077-5174 Sentence denotes The viral vector-based vaccines could also be quickly constructed and used without an adjuvant12.
T36 5175-5297 Sentence denotes However, development of such vaccines might not start until antigens containing the neutralizing epitopes are identified8.
T37 5298-5441 Sentence denotes The E and M proteins have important functions in the viral assembly of a coronavirus, and the N protein is necessary for viral RNA synthesis13.
T38 5442-5639 Sentence denotes Deletion of E protein abrogated the virulence of CoVs, and several studies have explored the potential of recombinant SARS-CoV or MERS-CoV with a mutated E protein as live attenuated vaccines13,14.
T39 5640-5959 Sentence denotes The M protein can augment the immune response induced by N protein DNA vaccine against SARS-CoV;15 however, the conserved N protein across CoV families implies that it is not a suitable candidate for vaccine development, and the antibodies against the N protein of SARS-CoV-2 do not provide immunity to the infection16.
T40 5960-6047 Sentence denotes The critical glycoprotein S of SARS-CoV-2 is responsible for virus binding and entry16.
T41 6048-6161 Sentence denotes The S precursor protein of SARS-CoV-2 can be proteolytically cleaved into S1 (685 aa) and S2 (588 aa) subunits10.
T42 6162-6273 Sentence denotes The S2 protein is well conserved among SARS-CoV-2 viruses and shares 99% identity with that of bat SARS-CoVs10.
T43 6274-6401 Sentence denotes The vaccine design based on the S2 protein may boost the broad-spectrum antiviral effect and is worth testing in animal models.
T44 6402-6590 Sentence denotes Antibodies against the conserved stem region of influenza hemagglutinin have been found to exhibit broadly cross-reactive immunity, but are less potent in neutralizing influenza A virus17.
T45 6591-6781 Sentence denotes In contrast, the S1 subunit consists of the receptor-binding domain (RBD), which mediates virus entry into sensitive cells through the host angiotensin-converting enzyme 2 (ACE2) receptor18.
T46 6782-6865 Sentence denotes The S1 protein of 2019-nCoV shares about 70% identity with that of human SARS-CoVs.
T47 6866-7048 Sentence denotes The highest number of variations of amino acids in the RBD is located in the external subdomain, which is responsible for the direct interaction between virus and host receptor10,18.
T48 7049-7155 Sentence denotes Blocking the initial entry of a virus is proposed as a successful strategy in controlling viral infection.
T49 7156-7349 Sentence denotes Based on SARS vaccine development, most vaccine candidates target the S protein, which induces neutralizing antibody responses and stimulates a protective cellular immunity against SARS-CoVs12.
T50 7350-7524 Sentence denotes Bukreyev et al.19 showed that immunization of African green monkeys with the full-length S protein of SARS-CoV protects monkeys from subsequent homologous SARS-CoV challenge.
T51 7525-7672 Sentence denotes Administration of SARS-CoV RBD proteins can also induce highly potent neutralizing antibodies and long-term protective immunity in animal models20.
T52 7673-7874 Sentence denotes Thus, the generation of antibodies targeting the S1 subunit of SARS-CoV-2 would be an important preventive and treatment strategy that can be tested further in suitable models before clinical trials10.
T53 7875-8008 Sentence denotes Vaccine delivery modality and immunization strategy are important issues to be considered for achieving effective antiviral immunity.
T54 8009-8264 Sentence denotes As a cause of respiratory tract infection and as demonstrated by the findings of SARS-CoV-2 in stools1,21, administration of vaccines by oral or aerosol routes will induce mucosal immune responses and are possible modes of SARS-CoV-2 vaccine immunization.
T55 8265-8547 Sentence denotes A safe DNA vector for preparation of DNA vaccines22, an attenuated virus strain for design of chimeric viral vaccines23, and engineered safe bacteria for production of membrane vesicle-vaccines24 could be explored for vaccine delivery and are worth investigating in the near future.
T56 8548-8633 Sentence denotes We can assume that virus-based vaccines should prove valuable in combatting COVID-19.
T57 8634-8854 Sentence denotes In addition to the entire virus particle-associated inactivated or attenuated viral vaccines, the subunit candidates, such as S1 protein and/or the RBD element of SARS-CoV-2, are also valuable targets for vaccine design.
T58 8855-9147 Sentence denotes Combining subunit vaccines with established or new adjuvants such as alum versus modern adjuvants such as the GSK AS series of adjuvants may represent a faster and safer strategy to move through early clinical development with the caveat that the protective efficacy may not be strong enough.
T59 9148-9305 Sentence denotes As a result, immunizing the subunit vaccines with proper delivery platforms and immunization strategies to enhance the immune responses should be considered.
T60 9306-9466 Sentence denotes We expect researchers who are racing against time will bring a new SARS-CoV-2-based vaccine from gene sequence to clinical testing in approximately 16–20 weeks.
T61 9468-9603 Sentence denotes Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
T62 9605-9621 Sentence denotes Acknowledgements
T63 9622-9801 Sentence denotes This work was supported by the National Key Biosafety Technology Research and Development Program of China (2017YFC1200404-4), and the Biosafety Research Program of PLA (17SAZ08).
T64 9803-9823 Sentence denotes Author contributions
T65 9824-9896 Sentence denotes W.S. and Y.R. wrote the manuscript: Y.Y. and X.R. edited the manuscript.
T66 9898-9917 Sentence denotes Competing interests
T67 9918-9961 Sentence denotes The authors declare no competing interests.