Prevention of Respiratory Syncytial Virus Infection in Healthy Adults by a Single Immunization of Ad26.RSV.preF in a Human Challenge Study.
Pre-F protein
RSV fusion protein
adenoviral vectors
adults
challenge study
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:
26 08 2022
26 08 2022
Historique:
received:
12
11
2020
accepted:
04
01
2021
pubmed:
6
1
2021
medline:
31
8
2022
entrez:
5
1
2021
Statut:
ppublish
Résumé
Respiratory syncytial virus (RSV) is a significant cause of severe lower respiratory tract disease in children and older adults, but has no approved vaccine. This study assessed the potential of Ad26.RSV.preF to protect against RSV infection and disease in an RSV human challenge model. In this double-blind, placebo-controlled study, healthy adults aged 18-50 years were randomized 1:1 to receive 1 × 1011 vp Ad26.RSV.preF or placebo intramuscularly. Twenty-eight days postimmunization, volunteers were challenged intranasally with RSV-A (Memphis 37b). Assessments included viral load (VL), RSV infections, clinical symptom score (CSS), safety, and immunogenicity. Postchallenge, VL, RSV infections, and disease severity were lower in Ad26.RSV.preF (n = 27) vs placebo (n = 26) recipients: median VL area under the curve (AUC) quantitative real-time polymerase chain reaction: 0.0 vs 236.0 (P = .012; predefined primary endpoint); median VL-AUC quantitative culture: 0.0 vs 109; RSV infections 11 (40.7%) vs 17 (65.4%); median RSV AUC-CSS 35 vs 167, respectively. From baseline to 28 days postimmunization, geometric mean fold increases in RSV A2 neutralizing antibody titers of 5.8 and 0.9 were observed in Ad26.RSV.preF and placebo, respectively. Ad26.RSV.preF was well tolerated. Ad26.RSV.preF demonstrated protection from RSV infection through immunization in a human challenge model, and therefore could potentially protect against natural RSV infection and disease. NCT03334695; CR108398, 2017-003194-33 (EudraCT); VAC18193RSV2002.
Sections du résumé
BACKGROUND
Respiratory syncytial virus (RSV) is a significant cause of severe lower respiratory tract disease in children and older adults, but has no approved vaccine. This study assessed the potential of Ad26.RSV.preF to protect against RSV infection and disease in an RSV human challenge model.
METHODS
In this double-blind, placebo-controlled study, healthy adults aged 18-50 years were randomized 1:1 to receive 1 × 1011 vp Ad26.RSV.preF or placebo intramuscularly. Twenty-eight days postimmunization, volunteers were challenged intranasally with RSV-A (Memphis 37b). Assessments included viral load (VL), RSV infections, clinical symptom score (CSS), safety, and immunogenicity.
RESULTS
Postchallenge, VL, RSV infections, and disease severity were lower in Ad26.RSV.preF (n = 27) vs placebo (n = 26) recipients: median VL area under the curve (AUC) quantitative real-time polymerase chain reaction: 0.0 vs 236.0 (P = .012; predefined primary endpoint); median VL-AUC quantitative culture: 0.0 vs 109; RSV infections 11 (40.7%) vs 17 (65.4%); median RSV AUC-CSS 35 vs 167, respectively. From baseline to 28 days postimmunization, geometric mean fold increases in RSV A2 neutralizing antibody titers of 5.8 and 0.9 were observed in Ad26.RSV.preF and placebo, respectively. Ad26.RSV.preF was well tolerated.
CONCLUSIONS
Ad26.RSV.preF demonstrated protection from RSV infection through immunization in a human challenge model, and therefore could potentially protect against natural RSV infection and disease.
CLINICAL TRIALS REGISTRATION
NCT03334695; CR108398, 2017-003194-33 (EudraCT); VAC18193RSV2002.
Identifiants
pubmed: 33400792
pii: 6064820
doi: 10.1093/infdis/jiab003
pmc: PMC9417128
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Respiratory Syncytial Virus Vaccines
0
Viral Fusion Proteins
0
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
396-406Informations de copyright
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
J Virol. 2011 May;85(9):4222-33
pubmed: 21325402
N Engl J Med. 2013 Dec 26;369(26):2481-91
pubmed: 24328444
J Infect Dis. 2020 Aug 17;222(6):979-988
pubmed: 32320465
J Infect Dis. 2015 Oct 15;212(8):1237-40
pubmed: 25904604
Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13239-13244
pubmed: 27799521
Curr Top Microbiol Immunol. 2013;372:83-104
pubmed: 24362685
Open Forum Infect Dis. 2017 Jan 09;4(1):ofw270
pubmed: 28480262
J Infect Dis. 2017 Dec 12;216(11):1362-1370
pubmed: 29029260
J Infect Dis. 2017 Feb 15;215(4):510-517
pubmed: 28329311
Lancet. 2017 Sep 2;390(10098):946-958
pubmed: 28689664
Science. 2019 Aug 2;365(6452):505-509
pubmed: 31371616
N Engl J Med. 2014 Aug 21;371(8):711-22
pubmed: 25140957
Epidemiol Infect. 2007 Oct;135(7):1099-108
pubmed: 17291381
Am J Respir Crit Care Med. 2010 Nov 15;182(10):1305-14
pubmed: 20622030
Open Forum Infect Dis. 2019 Apr 02;6(4):ofz159
pubmed: 31041354
N Engl J Med. 2015 Nov 19;373(21):2048-58
pubmed: 26580997
Clin Infect Dis. 2019 Jul 2;69(2):197-203
pubmed: 30452608
J Infect Dis. 2015 Dec 1;212(11):1719-25
pubmed: 25977264
Nat Commun. 2015 Sep 03;6:8143
pubmed: 26333350
Sci Immunol. 2016 Dec 16;1(6):
pubmed: 28111638
J Infect Dis. 2012 Oct;206(8):1250-9
pubmed: 22904335
Vaccine. 1999 Dec 10;18(9-10):899-906
pubmed: 10580204
J Infect Dis. 2013 Jan 15;207(2):248-56
pubmed: 23125443
Am J Epidemiol. 2008 Apr 1;167(7):775-85
pubmed: 18230677
Science. 2015 Jul 17;349(6245):320-4
pubmed: 26138104
J Infect Dis. 2020 Oct 7;222(Suppl 7):S577-S583
pubmed: 30880339
N Engl J Med. 2005 Apr 28;352(17):1749-59
pubmed: 15858184
Sci Transl Med. 2015 Oct 14;7(309):309ra162
pubmed: 26468324
PLoS One. 2014 Nov 21;9(11):e113100
pubmed: 25415360