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Combination Ad26.RSV.preF/preF protein vaccine induces superior protective immunity compared with individual vaccine components in preclinical models.

ABSTRACT: Respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously shown that a prefusion (preF) conformation-stabilized RSV F protein antigen and an adenoviral vector encoding RSV preF protein (Ad26.RSV.preF) are immunogenic and protective in animals when administered as single components. Here, we evaluated a combination of the 2 components, administered as a single injection. Strong induction of both humoral and cellular responses was shown in RSV-naïve and pre-exposed mice and pre-exposed African green monkeys (AGMs). Both components of the combination vaccine contributed to humoral immune responses, while the Ad26.RSV.preF component was the main contributor to cellular immune responses in both mice and AGMs. Immunization with the combination elicited superior protection against RSV A2 challenge in cotton rats. These results demonstrate the advantage of a combination vaccine and support further clinical development.

SUBMITTER: Saeland E

PROVIDER: S-EPMC10033289 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Combination Ad26.RSV.preF/preF protein vaccine induces superior protective immunity compared with individual vaccine components in preclinical models.

Saeland Eirikur E van der Fits Leslie L Bolder Renske R Heemskerk-van der Meer Marjolein M Drijver Joke J van Polanen Yolinda Y Vaneman Cornelis C Tettero Lisanne L Cox Freek F Serroyen Jan J Jorgensen Matthew J MJ Langedijk Johannes P M JPM Schuitemaker Hanneke H Callendret Benoit B Zahn Roland C RC

NPJ vaccines 20230323 1

Respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously shown that a prefusion (preF) conformation-stabilized RSV F protein antigen and an adenoviral vector encoding RSV preF protein (Ad26.RSV.preF) are immunogenic and protective in animals when administered as single components. Here, we evaluated a combination of the 2 components, administered as a single injection. Strong induction of both humoral and ce ...[more]

PMID: 36949051

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Project description:Abstract Background Respiratory syncytial virus (RSV) can cause serious lower respiratory tract disease (LRTD) among older adults. There is no licensed RSV vaccine. In CYPRESS (a randomized, double-blind, placebo-controlled, phase 2b proof-of concept trial; NCT03982199), an Ad26.RSV.preF/RSV preF protein vaccine demonstrated 80.0% efficacy for prevention of RSV LRTD and 69.8% efficacy for prevention of any RSV acute respiratory infection in adults aged ≥65 years through the first RSV season. This study evaluated the durability of immune responses elicited by Ad26.RSV.preF/RSV preF protein after two RSV seasons (up to 1.5 years post-vaccination) in the overall study population and in groups of participants stratified by age and risk level for severe RSV LRTD. Methods Participants (N=5782) were randomized 1:1 to receive vaccine or placebo before the RSV season. The primary endpoint was first occurrence of RSV LRTD. RSV A2 virus neutralizing antibodies (VNAs; through Day 365), RSV preF binding antibodies (through Day 533), and RSV-F–specific IFN-γ enzyme-linked immune absorbent spot (ELISpot; through Day 533), were evaluated in an immunogenicity subset (n=195; ages 65–74 years: n=141; 75–84 years: n=47; ≥85 years: n=6; increased risk [chronic heart or lung disease]: n=48; non-increased risk: n=147). Results In the vaccine group of the immunogenicity subset, RSV A2 VNAs peaked at Day 15 and were maintained at 2.8-fold over baseline at 1 year. Similarly, RSV preF-specific binding antibodies peaked at Day 15 and were maintained at 2.1-fold above baseline at 1.5 years. Median RSV-F–specific IFN-γ T-cell frequency increased from 34 spot-forming cells (SFC)/106 peripheral blood mononuclear cells (PBMCs) at baseline to 143 SFC/106 PBMCs at 1.5 years. Comparable immune responses were observed in age/risk subgroups. No relevant changes were observed in the placebo group at any time point. Pre-existing Ad26 VNAs did not appear to impact RSV-specific immune response durability. Conclusion Ad26.RSV.preF/RSV preF protein vaccine was efficacious and elicited robust, durable (to at least 1.5 years) humoral and cellular immune responses in adults aged ≥65 years, older participants (≥75 years), and in participants with increased risk for severe RSV LRTD. Disclosures Christy A. Comeaux, MD, PhD, Janssen Vaccines & Prevention B.V.: Employee Ann R. Falsey, MD, BioFire Diagnostics: Grant/Research Support|Janssen: Grant/Research Support|Merck Sharp & Dohme: Grant/Research Support|Novavax: Advisor/Consultant|Pfizer: Grant/Research Support Kristi Williams, PhD, Janssen Research and Development: Employee John E. Ervin, MD, The Alliance for Multispecialty Research – KCM: Contractual agreement for conduct of study protocol Arangassery R. Bastian, PhD, Janssen Vaccines & Prevention BV: Employee Joris Menten, PhD, Janssen Infectious Diseases: Employee Els De Paepe, MSc, Janssen Infectious Diseases: employee Sjouke Vandenberghe, PhD, Janssen Infectious Diseases: Employee Eric K. H. Chan, PhD, Janssen Global Services, LLC: Employee Jerald Sadoff, MD, Janssen Vaccines & Prevention BV: Employee Macaya Douoguih, MD, MPH, Janssen Vaccines & Prevention B.V.: Employee Benoit Callendret, PhD, Janssen Vaccines & Prevention B.V.: Employee Esther Heijnen, MD, PhD, Janssen Vaccines & Prevention B.V.: Employee.

Dataset Information

Combination Ad26.RSV.preF/preF protein vaccine induces superior protective immunity compared with individual vaccine components in preclinical models.

Publications

Combination Ad26.RSV.preF/preF protein vaccine induces superior protective immunity compared with individual vaccine components in preclinical models.

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