Epistemic_Statements  

CORD-19:0980c3bcb4bd20477b7fa0e3ffe668d9cf601af8 JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
T1 0-105 Epistemic_statement denotes Evaluation of two chimeric bovine-human parainfluenza virus type 3 vaccines in infants and young children
T2 116-285 Epistemic_statement denotes Human parainfluenza virus type 3 (HPIV3) is an important cause of lower respiratory tract illness in children, yet a licensed vaccine or antiviral drug is not available.
T3 1079-1200 Epistemic_statement denotes Taken together, these data suggest that the rB/HPIV3 vaccine is the preferred candidate for further clinical development.
T4 1438-1647 Epistemic_statement denotes [1] [2] [3] [4] [5] [6] Like respiratory syncytial virus (RSV), HPIV3 can cause bronchiolitis, viral pneumonia and apnea in infants and has been associated with wheezing episodes in older children with asthma.
T5 1648-1893 Epistemic_statement denotes [4, 5, [7] [8] [9] Although precise estimates do not exist, the outpatient burden of HPIV3 is likely substantial, since the number of emergency room and outpatient visits for HPIV3-associated illness may exceed hospitalizations by 10 to 80-fold.
T6 1894-2094 Epistemic_statement denotes [4, 6] Since approximately two-thirds of HPIV3 hospitalizations occur in the first year of life [4, 6] , development of a vaccine capable of inducing protective immunity in infancy is urgently needed.
T7 2095-2572 Epistemic_statement denotes Live-attenuated, intranasally-administered HPIV3 offers several potential advantages as a vaccine for infants, including ease of administration, reduction of the likelihood of interference with the many childhood vaccines that are given parenterally during the first year of life, lack of restriction of vaccine virus replication by the presence of HPIV3-specific maternal serum antibodies that are present in early infancy [10, 11] , and induction of local immunity [12, 13] .
T8 2573-2839 Epistemic_statement denotes Since the immunogenicity of vaccines administered during the first few months of life is typically less than that observed in older children, more than one dose of an HPIV3 vaccine would likely be needed to induce lasting protective immunity in infants and children.
T9 3040-3219 Epistemic_statement denotes [7] [ [16] [17] [18] [19] [20] The roles of other aspects of host immunity in protective responses against HPIV3 are not well understood, particularly in the pediatric population.
T10 3220-3302 Epistemic_statement denotes Two approaches have been used to generate HPIV3 vaccines for clinical development.
T11 4248-4367 Epistemic_statement denotes BPIV3 has been shown to be well-tolerated and attenuated in adults, children, and infants as young as one month of age.
T12 4928-5248 Epistemic_statement denotes Previous studies in non-human primates demonstrated that each of the genes of BPIV3 independently contributes to the host-range attenuation phenotype [20] , which suggested that chimeric human/bovine PIV3 vaccines could be developed to contain either a single BPIV3 gene substitution or multiple BPIV3 attenuating genes.
T13 11215-11483 Epistemic_statement denotes As part of the rB/HPIV3 study, an additional clinical assessment and a nasal wash were performed on day 28, and a follow-up phone call was conducted approximately 6 months after vaccination to determine whether any SAEs had occurred after the acute observation period.
T14 16130-16256 Epistemic_statement denotes Taken together, these data suggest that these vaccines are poorly infectious and immunogenic in HPIV3-experienced populations.
T15 17180-17395 Epistemic_statement denotes However, the mean duration of vaccine virus shedding was significantly greater in seronegative recipients of rHPIV3-N B than in seronegative recipients of rB/HPIV3 (14.7 vs. 8.2 days, P=.009; Table 1 and Figure 2 ).
T16 17849-18251 Epistemic_statement denotes While this child did shed vaccine virus on study days 3 through 7, vaccine virus was not detected in nasal wash specimens on subsequent days and in particular not at the time of the LRI (day 21); however, human metapneumovirus, bocavirus and coronavirus were detected in nasal washes obtained at that time, suggesting that a community-acquired infection was the most likely cause of the LRI (Table 1) .
T17 18835-19051 Epistemic_statement denotes Of note, the mean reciprocal log 2 serum HAI antibody titer in recipients of a single dose of 10 5.0 TCID 50 was significantly higher in rB/HPIV3 vaccinees than in rHPIV3-N B vaccinees (5.6 vs. 4.3, P=.01, Table 2 ).
T18 19598-19881 Epistemic_statement denotes [10] [21] In the majority of children over 6 months of age, experimental BPIV3 vaccines also elicited serum HAI antibody responses to the BPIV3 HN glycoprotein, the major viral protective antigen; however, very few of these children developed high titers of antibody to the HPIV3 HN.
T19 19882-20188 Epistemic_statement denotes This result was consistent with cross-neutralization studies that demonstrated only 25% antigenic relatedness between BPIV3 and HPIV3 HN and F [28] [29] , and suggested that inclusion of the HN and F glycoproteins from HPIV3 would be important for induction of antibodies against these protective antigens.
T20 21000-21111 Epistemic_statement denotes Interestingly, however, replication of these two experimental vaccines differed in HPIV3 seronegative children.
T21 21583-21955 Epistemic_statement denotes While replication of both rHPIV3-N B and rB/HPIV3 was restricted compared to what we have previously observed in children naturally infected with wt HPIV3 [11] , this study underscores the need for careful stepwise evaluation in susceptible pediatric populations to uncover subtle differences that may not be apparent when these viruses are evaluated in nonhuman primates.
T22 21956-22145 Epistemic_statement denotes Despite being more restricted in replication, the rB/HPIV3 vaccine induced significantly higher titers of HAI antibody than the rHPIV3-N B vaccine (5.6 vs. 4.3 reciprocal mean log 2 titer).
T23 22146-22199 Epistemic_statement denotes The reasons for this apparent difference are unclear.
T24 22200-22483 Epistemic_statement denotes One potential explanation for this observation might be that the BPIV3-specific accessory P gene products encoded by the rB/ HPIV3 vaccine are less able to inhibit human interferon induction and signaling than are the HPIV3-specific P gene products encoded by the rHPIV3-N B vaccine.
T25 22484-22768 Epistemic_statement denotes Greater interferon production and signaling in response to the rB/HPIV3 vaccine might have adjuvant effects resulting in a stronger antibody response, as has been noted in bovines infected with bovine RSV mutants that differed in their ability to control the host interferon response.
T26 22769-22956 Epistemic_statement denotes [30] In any case, the combination of greater restriction in replication with increased antibody response makes the rB/HPIV3 vaccine a more promising candidate than the rHPIV3-N B vaccine.
T27 22957-23433 Epistemic_statement denotes The titer of antibody achieved in HPIV3 seronegative children after a single dose of rB/HPIV3 vaccine was only slightly lower than that measured in seropositive children who had presumably experienced prior infection with wt HPIV3 (Table 2) , and, since more than one dose of this vaccine would likely be administered [31] , it is possible than antibody titers comparable to infection with wt HPIV3 might be achieved following completion of a vaccination series with rB/HPIV3.
T28 23434-23543 Epistemic_statement denotes The tolerability of these vaccines was difficult to assess completely in these small phase I clinical trials.
T29 23544-23636 Epistemic_statement denotes Importantly, LRI and/or other SAEs associated with vaccine virus shedding were not observed.
T30 23822-23984 Epistemic_statement denotes These types of illnesses often occur in infants and preschoolers and can confound the assessment of reactogenicity of a live-attenuated respiratory virus vaccine.
T31 23985-24332 Epistemic_statement denotes In particular, assessing the causal relationship between vaccine administration and a mild illness such as rhinorrhea will require studies in larger numbers of children: for example, the association between the live-attenuated influenza vaccine FluMist and mild upper respiratory symptoms was not apparent until large-scale studies were completed.
T32 24333-24506 Epistemic_statement denotes [32] If the rB/HPIV3 vaccine undergoes further clinical development, additional information regarding the safety and reactogenicity of this vaccine will need to be obtained.
T33 24639-24808 Epistemic_statement denotes Of the two vaccines, rB/HPIV3 appears to be both more restricted in replication and more immunogenic, making it the preferred candidate for further clinical development.
T34 24809-25031 Epistemic_statement denotes Currently, a live-attenuated HPIV3 vaccine (cp45 and the recombinant version, rcp45) has been shown to be highly attenuated, infectious and immunogenic in phase I and II clinical trials in HPIV3-naïve infants and children.
T35 25032-25183 Epistemic_statement denotes [11] [33] [34] rB/HPIV3 represents a potential additional liveattenuated investigational HPIV3 vaccine that could be evaluated in phase II/III studies.
T36 25184-25363 Epistemic_statement denotes Alternatively, rB/HPIV3 could be used to express the surface glycoproteins of related paramyxoviruses that are important pediatric pathogens, such as RSV or human metapneumovirus.
T37 26707-26868 Epistemic_statement denotes This participant was inoculated in September and may have been infected with wild-type HPIV3 before collection of the postinoculation serum specimen in November.