A Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine With and Without Adjuvant in Healthy Older Adults.
RSV
prefusion F subunit
respiratory syncytial virus
vaccine
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
13 12 2022
13 12 2022
Historique:
received:
20
12
2021
accepted:
09
05
2022
pubmed:
12
5
2022
medline:
16
12
2022
entrez:
11
5
2022
Statut:
ppublish
Résumé
Respiratory syncytial virus (RSV) is an important cause of disease in older adults. We evaluated the safety and immunogenicity of a stabilized RSV prefusion F subunit (RSVpreF) vaccine candidate with/without adjuvant in adults aged 65-85 years. Primary cohort participants were equally randomized to 1 of 7 RSVpreF formulations: 60 µg with either Al(OH)3 or CpG/Al(OH)3, 120 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg unadjuvanted, or placebo, administered concomitantly with high-dose seasonal inactivated influenza vaccine (SIIV). Participants in the month 0,2 cohort were randomized to RSVpreF 240 µg with CpG/Al(OH)3 or placebo, administered at months 0 and 2. All RSVpreF vaccine candidates elicited robust and persistent serum neutralizing responses when administered alone or with SIIV. There was no notable difference in neutralizing response between the formulations, including those containing CpG. In the month 0,2 cohort, there was no booster effect of dose 2. SIIV responses were similar or slightly lower with concomitant administration of RSVpreF. Most systemic and local reactions were mild and more frequent after RSVpreF than placebo. RSVpreF formulations were well tolerated and elicited robust neutralizing responses in older adults; however, CpG/Al(OH)3 did not further enhance responses. Clinical Trials Registration. NCT03572062.
Sections du résumé
BACKGROUND
Respiratory syncytial virus (RSV) is an important cause of disease in older adults. We evaluated the safety and immunogenicity of a stabilized RSV prefusion F subunit (RSVpreF) vaccine candidate with/without adjuvant in adults aged 65-85 years.
METHODS
Primary cohort participants were equally randomized to 1 of 7 RSVpreF formulations: 60 µg with either Al(OH)3 or CpG/Al(OH)3, 120 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg unadjuvanted, or placebo, administered concomitantly with high-dose seasonal inactivated influenza vaccine (SIIV). Participants in the month 0,2 cohort were randomized to RSVpreF 240 µg with CpG/Al(OH)3 or placebo, administered at months 0 and 2.
RESULTS
All RSVpreF vaccine candidates elicited robust and persistent serum neutralizing responses when administered alone or with SIIV. There was no notable difference in neutralizing response between the formulations, including those containing CpG. In the month 0,2 cohort, there was no booster effect of dose 2. SIIV responses were similar or slightly lower with concomitant administration of RSVpreF. Most systemic and local reactions were mild and more frequent after RSVpreF than placebo.
CONCLUSIONS
RSVpreF formulations were well tolerated and elicited robust neutralizing responses in older adults; however, CpG/Al(OH)3 did not further enhance responses. Clinical Trials Registration. NCT03572062.
Identifiants
pubmed: 35543281
pii: 6583554
doi: 10.1093/infdis/jiac189
pmc: PMC9749002
doi:
Substances chimiques
Respiratory Syncytial Virus Vaccines
0
Viral Fusion Proteins
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Adjuvants, Immunologic
0
Adjuvants, Pharmaceutic
0
Banques de données
ClinicalTrials.gov
['NCT03572062']
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase II
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2054-2063Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Déclaration de conflit d'intérêts
Potential conflicts of interest . J. B., A. J., Q. J., K. S., D. C., M. M., J. L., A. G., K. J., W. G., P. D., and B. S.-T. are employees of Pfizer Inc and may hold Pfizer Inc stock or stock options. 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.
Références
Vaccine. 2017 Jan 23;35(4):513-520
pubmed: 28024956
MMWR Morb Mortal Wkly Rep. 2018 Apr 20;67(15):455-458
pubmed: 29672472
J Infect Dis. 2022 Aug 26;226(3):396-406
pubmed: 33400792
Immun Ageing. 2019 Sep 13;16:25
pubmed: 31528180
Immunol Lett. 2014 Nov;162(1 Pt B):346-53
pubmed: 24960535
J Infect Dis. 2017 Dec 12;216(11):1362-1370
pubmed: 29029260
Clin Infect Dis. 2014 Feb;58(3):342-9
pubmed: 24265361
Vaccine. 2014 Sep 3;32(39):5027-34
pubmed: 25045825
J Infect Dis. 2022 Apr 19;225(8):1357-1366
pubmed: 34932102
N Engl J Med. 2005 Apr 28;352(17):1749-59
pubmed: 15858184
Pediatrics. 2013 Aug;132(2):e341-8
pubmed: 23878043
Adv Ther. 2020 Mar;37(3):1203-1217
pubmed: 32026380
J Infect Dis. 2004 Jan 15;189(2):233-8
pubmed: 14722887
Vaccine. 2014 Nov 12;32(48):6377-89
pubmed: 24975812
Infect Dis Ther. 2021 Mar;10(Suppl 1):47-60
pubmed: 33656652
J Infect Dis. 2022 Jun 15;225(12):2056-2066
pubmed: 34931667