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Clinical Trial
. 2024 Jan 12;229(1):95-107.
doi: 10.1093/infdis/jiad271.

Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6-7 Months of age: A Phase 1/2 Randomized Trial

Xavier Sáez-Llorens  1   2   3   4 , Ximena Norero  1   2 , Marisa Márcia Mussi-Pinhata  5 , Kathia Luciani  6 , Ignacio Salamanca de la Cueva  7 , Javier Díez-Domingo  8 , Eduardo Lopez-Medina  9 , Cristina Epalza  10 , Jerzy Brzostek  11 , Henryk Szymański  12 , François D Boucher  13 , Benhur S Cetin  14 , Tirza De Leon  15 , Ener Cagri Dinleyici  16 , Miguel Ángel Marín Gabriel  17 , Tolga Ince  18 , Mercedes Macias-Parra  19 , Joanne M Langley  20 , Federico Martinón-Torres  21   22   23 , Mika Rämet  24 , Ernest Kuchar  25 , Jorge Pinto  26 , Thanyawee Puthanakit  27 , Fernando Baquero-Artigao  28 , Guido Castelli Gattinara  29 , Jose Manuel Merino Arribas  30 , Jose Tomas Ramos Amador  31   32 , Leszek Szenborn  33 , Bruce Tapiero  34 , Evan J Anderson  35 , James D Campbell  36 , Saul N Faust  37 , Vanja Nikic  38 , Yingjun Zhou  38 , Wenji Pu  38 , Damien Friel  39 , Ilse Dieussaert  39 , Antonio Gonzalez Lopez  38 , Roderick McPhee  38 , Sonia K Stoszek  38 , Nicolas Vanhoutte  39
Affiliations
Clinical Trial

Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6-7 Months of age: A Phase 1/2 Randomized Trial

Xavier Sáez-Llorens et al. J Infect Dis. .

Abstract

Background: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants.

Methods: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years.

Results: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2.

Conclusions: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.

Keywords: ChAd155; RSV; immunogenicity; infant; vaccine-associated enhanced respiratory disease.

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Conflict of interest statement

Potential conflicts of interest. V. N., Y. Z., W. P., D. F., I. D., A. G. L., R. M., S. K. S., and N. V. are or were employees of GSK during the conduct of the study. I. D., W. P., and S. K. S. hold GSK shares/stocks. R. M. and S. K. S. hold stock/stock options in Moderna. B. T., E. J. A., B. S. C., E. C. D., H. S., J. D. C., J. M. M. A., K. L., M. M. M.-P., M. R., S. N. F., F. B.-A., and T. P. report grants and/or other support from GSK for the conduct of the study. J. M. L. reports grants from GSK paid to her institution for the conduct of the study and holds the CIHR-GSK Chair in Pediatric Vaccinology at Dalhousie University. B. T. reports grants from GSK, Merck, and Pfizer for other trials. C. e. reports support for scientific meetings from GSK and ViiV and advisory consultancy fees from GSK. E. J. A. has consulted for Pfizer, Sanofi Pasteur, GSK, Janssen, Moderna, and Medscape, and his institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Novavax, Sanofi Pasteur, Janssen, and Micron; he serves on a safety monitoring board for Kentucky BioProcessing and Sanofi Pasteur; serves on a data adjudication board for WCG and ACI Clinical; and his institution has also received funding from the National Institutes of Health to conduct clinical trials of COVID-19 vaccines. B. S. C. reports grants for other vaccine trials from GSK and MSD paid to his institution. E. C. D. performs contract work for the Eskisehir Osmangazi University funded by GSK, Sanofi Pasteur, and Pfizer. E. K. reports honoraria for lectures from GSK, MSD, AstraZeneca, Sanofi, and Pfizer. E. L.-M. reports grants from Centro de Estudios en Infectología Pediátrica. F. M.-T. reports grants from Janssen, MSD, and AstraZeneca; personal fees from Ablynx, GSK, Pfizer, MSD, Sanofi Pasteur, Novavax, Seqirus, and Biofabri; nonfinancial support from GSK, Pfizer, MSD, and Seqirus; and trial fees paid to his institution from these different companies (except Biofabri). H. S. reports personal fees and trial fees paid to his institution from MSD, Seqirus, Pfizer, Janssen, and Sanofi Pasteur. I. S. C. has received payment to his institution from GSK for the conduct of the study, by contract approved by the corresponding ethical committees and health authorities, and for trials of other vaccine manufacturers, and has received grants and/or honoraria as a consultant/advisor/speaker or for attending conferences and practical courses from GSK and other vaccine manufacturers. J. D. C. is a member of the Committee on Infectious Diseases of the American Academy of Pediatrics and reports funds paid to his university to study RSV vaccines. J. D.-D. reports grants from GSK, MSD, and Sanofi Pasteur paid to his institution. J. M. M. A. reports fees for medical meetings from GSK and Pfizer. K. L. reports grants from ReViral and Shionogi. M. M.-P. reports grants from MSD, Roche, GSK, Janssen, Takeda, and Syneos. M. R. reports grants for other vaccine trials from GSK and other vaccine manufacturers paid to his institution. S. N. F. reports fees paid to his institution for attending meetings, advisory boards, and/or grants for clinical trials from AstraZeneca/Medimmune, GSK, J&J, Pfizer, Sanofi, Seqirus, Sandoz, Valneva, Novavax, and Merck. X. S.-L. reports grants from Cevaxin Vaccine Research Center. F. B.-A. reports consultancy fees from GSK, Pfizer, and MSD and grants from MSD. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Study design. Abbreviations: 4CMenB, 4-component meningococcal serogroup B vaccine; comparator, group receiving either placebo as dose 1 and 2, or active comparator vaccine as dose 1 or 2 and placebo as the other dose (as indicated)—note, active comparators were given based on approved schedules; D, day; MenACWY-CRM, meningococcal serogroups A, C, W, Y CRM197 conjugate vaccine; MenACWY-TT, meningococcal serogroups A, C, W, Y tetanus toxoid conjugate vaccine; PHiD-CV, pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine; RSV, respiratory syncytial virus; RSV_1D, group receiving 1 low chimpanzee-derived replication-deficient adenoviral vector RSV vaccine (ChAd155-RSV) dose as dose 1 and placebo as dose 2; RSV_2D, group receiving 2 high ChAd155-RSV doses as dose 1 and 2.
Figure 2.
Figure 2.
Disposition of participants. aThe comparator group included 22 infants who received placebo only and 43 who received active comparator and placebo (29 received 4-component meningococcal serogroup B vaccine, 1 received meningococcal serogroups A, C, W, Y tetanus toxoid conjugate vaccine, 1 received pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine, and 12 received meningococcal serogroups A, C, W, Y CRM197 conjugate vaccine). bRSV-seronaive at screening, ie, RSV-A neutralizing titer <63.086 estimated dilution 60, which represents a titer 2-fold higher than the estimated RSV-A neutralizing titer in infants at 6 months of age due to residual maternal antibodies (based on modeling estimates). Abbreviations: comparator, group receiving either placebo as dose 1 and 2, or active comparator vaccine as dose 1 or 2 and placebo as the other dose (pooled); RSV, respiratory syncytial virus; RSV_1D, group receiving 1 low chimpanzee-derived replication-deficient adenoviral vector RSV vaccine (ChAd155-RSV) dose as dose 1 and placebo as dose 2; RSV_2D, group receiving 2 high ChAd155-RSV doses as dose 1 and 2; (S)AE, (serious) adverse event.
Figure 3.
Figure 3.
Solicited adverse events within 7 days after vaccination (exposed set). Error bars depict 95% confidence intervals. Graphs show the percentage of infants with solicited adverse events after at least 1 of the 2 doses (A), after dose 1 (B), and after dose 2 (C). Grade 3 was defined as follows: crying when the limb was moved/limb was spontaneously painful for pain; diameter >20 mm for erythema and swelling; not eating at all for loss of appetite; crying inconsolably/preventing normal activities for irritability; preventing normal activities for drowsiness; temperature >40°C for fever. Abbreviations: active comparator, group receiving active comparator vaccine as dose 1 or 2 and placebo as the other dose; n, total number of participants with available results; placebo, group receiving placebo as dose 1 and 2; RSV, respiratory syncytial virus; RSV_1D, group receiving 1 low chimpanzee-derived replication-deficient adenoviral vector RSV vaccine (ChAd155-RSV) dose as dose 1 and placebo as dose 2; RSV_2D, group receiving 2 high ChAd155-RSV doses as dose 1 and 2.
Figure 4.
Figure 4.
Respiratory syncytial virus (RSV)–A neutralizing geometric mean titers (A) and RSV F-binding immunoglobulin G geometric mean concentrations (B) (per-protocol population of baseline RSV-seronaive infants). Error bars depict 95% confidence intervals. Abbreviations: comparator, group receiving either placebo as dose 1 and 2, or active comparator vaccine as dose 1 or 2 and placebo as the other dose (pooled); D31, 30 days postvaccination; D61, 60 days postvaccination; ED60, estimated dilution 60; EoS1, end of respiratory syncytial virus season 1; EU, enzyme-linked immunosorbent assay units; IgG, immunoglobulin G; n, total number of participants with available results at the indicated timepoint; RSV-A, respiratory syncytial virus subtype A; RSV_1D, group receiving 1 low chimpanzee-derived replication-deficient adenoviral vector RSV vaccine (ChAd155-RSV) dose as dose 1 and placebo as dose 2; RSV_2D, group receiving 2 high ChAd155-RSV doses as dose 1 and 2; RSV F, respiratory syncytial virus fusion protein.
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References

    1. Borchers AT, Chang C, Gershwin ME, Gershwin LJ. Respiratory syncytial virus—a comprehensive review. Clin Rev Allergy Immunol 2013; 45:331–79. - PMC - PubMed
    1. Obando-Pacheco P, Justicia-Grande AJ, Rivero-Calle I, et al. Respiratory syncytial virus seasonality: a global overview. J Infect Dis 2018; 217:1356–64. - PubMed
    1. Di Mattia G, Nenna R, Mancino E, et al. During the COVID-19 pandemic where has respiratory syncytial virus gone? Pediatr Pulmonol 2021; 56:3106–9. - PMC - PubMed
    1. Tang JW, Bialasiewicz S, Dwyer DE, et al. Where have all the viruses gone? Disappearance of seasonal respiratory viruses during the COVID-19 pandemic. J Med Virol 2021; 93:4099–101. - PMC - PubMed
    1. van Summeren J, Meijer A, Aspelund G, et al. Low levels of respiratory syncytial virus activity in Europe during the 2020/21 season: what can we expect in the coming summer and autumn/winter? Euro Surveill 2021; 26:2100639. - PMC - PubMed

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