A recent trial depicted that a single dose of Ad26.COV2.S (a recombinant, replication-incompetent human adenovirus type 26 vector that encodes full-length coronavirus spike protein in a prefusion-stabilized conformation) safeguarded against symptomatic COVID-19 and asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It also displayed efficacy against severe-critical viral infection, including mortality and hospitalization. This trial (ENSEMBLE) was carried out to examine the safety and efficacy of Ad26.COV2.S for preventing SARS-CoV-2 infection in adults.

The enrolled individuals were randomized to receive a single dose of Ad26.COV2.S (5×1010 viral particles, n=19,630) or placebo (n=19,691) in this randomized, phase III, international, double-blind, placebo-controlled trial. In the per-protocol population that tested negative for coronavirus infection,  the effectiveness of the vaccine against moderate to severe–critical viral infection with an onset at least 14 days and 28 days after treatment were the major outcomes. Evaluation of safety was also done.

The vaccine was found to safeguard against both moderate to severe–critical infection and severe–critical infection with onset at least 14 and 28 days after administration. The efficacy of the vaccine was higher with severe–critical coronavirus infection as depicted below: 

In South Africa, despite 94.5% (86/91) cases with the sequenced virus having the 20H/501Y.V2 variant, the efficacy of vaccine was greater against severe–critical infection compared to moderate to severe-critical infection, as illustrated in the table below: 

Compared to placebo, the vaccine displayed greater reactogenicity, but it was transient mild to moderate in severity. The occurrence of severe adverse effects was balanced between the two arms. Notably, three deaths were found to occur in the vaccine arm (none were coronavirus-related), and 16 deaths occurred in the placebo group (5 were coronavirus-related).

Safety was found to be similar to that noted in other phase III studies of coronavirus vaccines. Thus, Ad26.COV2.S appears to be a promising vaccine for managing coronavirus-infected patients.