Safety and immunogenicity of Ad26.COV2.S in adults: A randomised, double-blind, placebo-controlled Phase 2a dose-finding study.

Background: A single dose of Ad26.COV2.S is well-tolerated and effective in preventing moderate-to-severe disease outcomes due to COVID-19. We evaluated the impact of dose level, number of doses, and dose interval on immunogenicity, reactogenicity, and safety of Ad26.COV2.S in adults. Anamnestic responses were also explored.
Methods: This randomised, double-blind, placebo-controlled, Phase 2a study was conducted in adults aged 18-55 years and ≥ 65 years (NCT04535453). Four dose levels (1.25 × 10 ¹⁰ , 2.5 × 10 ¹⁰ , 5 × 10 ¹⁰ , and 1 × 10 ¹¹ viral particles [vp], single and 2-dose schedules, and dose intervals of 56 and 84 days, were assessed. Four or 6 months post-primary vaccination, Ad26.COV2.S 1.25 × 10 ¹⁰ vp was given to evaluate anamnestic responses. Humoral and cell-mediated immune responses were measured. Reactogenicity and safety were assessed in all participants.
Results: All Ad26.COV2.S schedules induced humoral responses with evidence of a dose response relationship. A single dose of Ad26.COV2.S (5 × 10 ¹⁰ vp) induced antibody and cellular immune responses that persisted for up to at least 6 months. In the 2-dose regimens, antibody responses were higher than 1-dose regimens at comparable dose levels, and the magnitude of the immune response increased when the interval between doses was increased (84 days vs 56 days). Rapid, marked immune responses were observed in all groups after vaccine antigen exposure indicating immune memory. Durable immune responses were observed in all groups for up to at least 6 months post-antigen exposure. Strong and consistent correlations between neutralising and binding antibodies were observed CD4 + and CD8 + T cell responses were similar after all regimens. Reactogenicity within 7 days post-vaccination tended to be dose-related.
Conclusion: The study supports the primary, single dose schedule with Ad26.COV2.S at 5 × 10 ¹⁰ vp and homologous booster vaccination after a 6 month interval. Rapid and marked responses to vaccine antigen exposure indicate induction of immune memory by 1- and 2-dose primary vaccination.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Vicky Cardenas reports financial support was provided by Johnson & Johnson. Mathieu Le Gars reports financial support was provided by Johnson & Johnson. Carla Truyers reports financial support was provided by Johnson & Johnson. Javier Ruiz-Guinazu reports financial support was provided by Johnson & Johnson. Frank Struyf reports financial support was provided by Johnson & Johnson. Alicia Colfer reports financial support was provided by Johnson & Johnson. Macaya Douoguih reports financial support was provided by Johnson & Johnson. Jerald Sadoff reports financial support was provided by Johnson & Johnson. Marc Bonten reports a relationship with Shionogi, Merck, GSK and Janssen Vaccines that includes: consulting or advisory. Marc Bonten reports a relationship with Sanofi that includes: board membership. Frank Struyf reports a relationship with GSK that includes: equity or stocks. Marc Bonten reports a relationship with Johnson & Johnson, Merck, Sanofi that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper].
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