Randomized Controlled Trial
Study population and setting
Reported are interim results of a randomized, double-blind, placebo controlled Phase 1/2a clinical trial of Ad26.COV2.S. Ad26.COV2.S is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding full-length SARS-CoV-2 spike protein developed and manufactured by Johnson and Johnson. The trial occurred at 12 centers in Belgium and the US. Healthy adults age 18-55 years were enrolled into cohort 1 and healthy adults 65 years and older were enrolled into cohort 3. Cohort 1 was divided into cohort 1a (with a target of 375 participants) and cohort 1b (with a target of 25 participants), with cohort 1b intended for an in-depth analysis of immunogenicity. Participants were administered either a high dose (1×10^11 viral particles) or a low dose (5×10^10 viral particles) in either a 1- or 2-dose regimen. Primary endpoints were safety and reactogenicity. The secondary endpoint was humoral and cellular immunity to the SARS-CoV-2 S protein. The study included people who were already seropositive for SARS-CoV-2 S-protein (2% in cohort 1a and 1% in cohort 3).
Summary of Main Findings
The most frequent adverse events reported were injection-site pain, fatigue, headache, and myalgia. Five serious adverse events occurred during the trial. Only one, fever resulting in hospitization, was deemed to be related to the vaccine. This patient recovered within 12 hours and continued with the trial. There was a trend towards higher incidence of adverse events in the high dose groups and a trend towards decreased adverse events with increasing age. Additionally, systemic adverse events were lower following the second dose compared with the first dose.
In cohort 1a, SARS-CoV-2 S-protein specific antibodies and neutralizing antibodies were detected in all groups at day 29 post-first dose with levels similar to that in human convalescent sera. Seroconversion was detected in 99-100% of participants across dose regimens with 100% of cohort 1a participants across all dose regimens seroconverting by day 57 post-vaccination. In cohort 3, SARS-CoV-2 S-protein specific antibodies and neutralizing antibodies were detected in all groups by day 15 post-vaccination, however antibody levels were lower than observed in human convalescent sera. Seroconversion was observed in 96% of the high and low dose groups in this cohort with 96% in the low dose group positive for neutralizing antibodies and 88% in the high dose group. CD4+ T-cell responses were also observed in all (76 to 83% in cohort 1 and 60 to 67% in cohort 3) with a clear bias towards a type 1 helper T cell response.
This study included separate analysis of elderly populations, which is important as this is a high risk population and immune response in this population is often decreased compared to younger populations. While there is no known correlate of protection, comparisons of antibody responses to convalescent plasma is a helpful way to gauge the strength of immune response induced by vaccination.
While data here is promising, there currently is no known correlate of protection for SARS-CoV-2. As such, the efficacy of this vaccine cannot be determined until ongoing phase 3 clinical trial data is reported. So far, data has only been collected post-first dose for the populations over 65. As this group had a lower overall immune response compared to the 18-55 year old cohort, it remains to be seen in a second dose can boost this response. The effect of the second dose in elderly populations is currently being studied in a phase 3 clinical trial. There is a lack of diversity in the trial demographics. This is being addressed in their ongoing phase 3 clinical trial.
This study demonstrates that this Ad26.COV2.S vaccine is safe and immunogenic after only one dose. A single dose vaccine has significant logistical advantages over the current 2-dose vaccines currently approved under Emergency Use Authorization.
This review was posted on: 19 January 2021