Open Access
LB14. Efficacy and Immunogenicity of an Ad26.RSV.preF-based Vaccine in the Prevention of RT-PCR-confirmed RSV-mediated Lower Respiratory Tract Disease in Adults Aged ≥65 Years: A Randomized, Placebo-controlled, Phase 2b Study
Author(s) -
Ann R. Falsey,
Kristi Williams,
Efi Gymnopoulou,
Stephan Bart,
John Ervin,
Arangassery Rosemary Bastian,
Joris Menten,
Els De Paepe,
H. D. Boer,
Sjoukje Vandenberghe,
Eric K. H. Chan,
Jerald Sadoff,
Macaya Douoguih,
Benoît Callendret,
Christy Comeaux,
Esther Heijnen
Publication year - 2021
Publication title -
open forum infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.546
H-Index - 35
ISSN - 2328-8957
DOI - 10.1093/ofid/ofab466.1650
Subject(s) - medicine , placebo , clinical endpoint , respiratory tract infections , lower respiratory tract infection , randomized controlled trial , immunogenicity , upper respiratory tract infection , immunology , respiratory system , antibody , pathology , alternative medicine
Abstract Background Respiratory syncytial virus (RSV) can cause serious lower respiratory tract disease (LRTD) in older adults. Despite a high burden of disease, there is currently no licensed vaccine for RSV. Here, we report the primary efficacy and immunogenicity results from a Phase 2b proof-of-concept trial of an Ad26.RSV.preF-based vaccine for the prevention of RSV-mediated LRTD in adults aged ≥65 years. Methods CYPRESS (NCT03982199) is a randomized, double-blind, placebo-controlled Phase 2b trial. Adults ≥65 years of age were randomized 1:1 prior to the RSV season to receive an Ad26.RSV.preF-based vaccine or placebo. Symptoms of acute respiratory infection (ARI) were collected through an RSV-specific patient-reported Respiratory Infection Intensity and Impact Questionnaire (RiiQ) and/or by a clinician assessment until the end of the RSV season. The primary endpoint was the first occurrence of RT-PCR-confirmed RSV-mediated LRTD according to any of 3 case definitions: (1) ≥3 symptoms of lower respiratory tract infection (LRTI), (2) ≥2 symptoms of LRTI, or (3) ≥2 symptoms of LRTI or ≥1 symptom of LRTI with ≥1 systemic symptom. The secondary endpoint was the first occurrence of any RT-PCR-confirmed RSV-mediated ARI. Immunogenicity assessments were performed in a subset of approximately 200 participants. Results A total of 5782 participants (2891 in each study arm) received study treatment (92.5% white, 57.7% female, median age 71 years). Vaccine efficacy was 80% (94.2% CI, 52.2–92.9%), 75% (50.1–88.5%), and 69.8% (43.7–84.7%) for case definition 1, 2, and 3, respectively (all P values < 0.001). Efficacy for any RSV-mediated ARI was 69.8% (95% CI, 42.7–85.1%). In the vaccine arm of the immunogenicity subset, geometric mean fold increase in antibody titers 14 days after vaccination was 13.5 for RSV neutralizing antibodies and 8.6 for RSV prefusion F-specific binding antibodies. Median frequency of RSV-F-specific INFγ T-cells increased from 34 to 444 SFC/10 6 PBMC 14 days after vaccination in the vaccine arm; no relevant changes were observed in the placebo arm. Conclusion In CYPRESS, the Ad26.RSV.preF-based vaccine was highly effective against RSV-mediated LRTD through the first RSV season and elicited robust humoral and cellular immune responses in adults aged ≥65 years. Disclosures Ann R. Falsey, MD , AstraZeneca (Individual(s) Involved: Self): Grant/Research Support; BioFire Diagnostics (Individual(s) Involved: Self): Grant/Research Support; Janssen (Individual(s) Involved: Self): Grant/Research Support; Merck, Sharpe and Dohme (Individual(s) Involved: Self): Grant/Research Support; Novavax (Individual(s) Involved: Self): Other Financial or Material Support, Paid DSMB member; Pfizer (Individual(s) Involved: Self): Grant/Research Support Kristi Williams, PhD , Janssen R&D US (Employee) Efi Gymnopoulou, MSc , Janssen Infectious Diseases BV (Employee) Arangassery Rosemary Bastian, PhD , Janssen Vaccines & Prevention BV (Employee) Joris Menten, n/a , Janssen Infectious Diseases BV (Employee) Els De Paepe, MSc , Janssen Infectious Diseases BV (Employee) Hilde de Boer, MSc , Janssen-Cilag (Employee) Sjoukje Vandenberghe, n/a , Janssen Infectious Diseases BV (Employee) Eric Chan, PhD , Janssen Global Services, LLC (Employee) Jerald Sadoff, MD , Johnson & Johnson (Employee, Shareholder) Macaya Douoguih, MD, MPH , Janssen (Employee) Benoit Callendret, PhD , Janssen Vaccines & Prevention BV (Employee) Christy Comeaux, MD , Janssen Vaccines & Prevention BV (Employee) Esther Heijnen, MD , Janssen Vaccines & Prevention BV (Employee)