Next in line in the armamentarium against COVID-19 is likely the single-dose Ad26.COV2.S vaccine, being developed by Johnson & Johnson/Janssen, anticipate infectious disease experts.

It got closer with promising interim phase 1/2a trial results that were published online January 13 in The New England Journal of Medicine.

A single Ad26.COV2.S dose was found to be associated with S-binding and neutralizing antibodies in over 90% of the participants. The finding was evident in both adults aged 18-55 years and participants 65 years and older, as well as in participants given low-dose or high-dose vaccinations.

The results also pointed to a durable vaccine response.

The take-home message is a high neutralizing antibody responder rate to a single dose of the Ad26.COV2.S COVID-19 vaccine candidate. These responses and antibody titers are stable for at least 71 days.

Another advantage is the need of less stringent storage requirements -only regular refrigeration vs a need to freeze the Pfizer/BioNTech and Moderna vaccines.

The Ad26.COV2.S vaccine can be refrigerated for up to 3 months at 2°-8 °C.

Johnson & Johnson vaccine is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike (S) protein.

The urgency of the COVID-19 pandemic hastened the vaccine development process; therefore, preclinical trials were conducted simultaneously and not sequentially. Phase 3 interim results for the Johnson & Johnson vaccine are expected within weeks, and the rollout is expected in March.

Investigators hope to report data from the first phase 3 study, ENSEMBLE, which tests the protective efficacy of a single dose of Ad26.COV2.S, by the end of this month or early February.

The phase 1/2a ongoing, multicenter, randomized, double-blind, and placebo-controlled trial interim results are highly encouraging and support the single inoculation approach. It shows solid antibody, CD4 T cell, and CD8 T cell responses.

At baseline for the phase 1/2a trial, 2% of the younger group and 1% of the 65+ group were seropositive for SARS-CoV-2 S-specific antibodies.

Overall, 402 people in the younger age cohort and 403 in the 65 and older group were given a first dose of the Johnson & Johnson vaccine. Many participants also received a second dose after a gap of 56 days for a separate trial, ENSEMBLE2, which compares safety and efficacy between single- and double-dose regimens. Results of that trial are pending.

A single dose was shown to be associated with a higher incidence of solicited systemic adverse events in the higher vaccine dose group. Grade 3 adverse events decreased with increasing age.

Injection site pain on the day of immunization or the next day was the commonest local reaction. The pain generally resolved within 24 hours. Fever was reported by 15% in the low-dose vaccine group and 39% in the high-dose group. The most common grade 1 or 2 solicited systemic adverse events reported included fatigue, headache, and myalgia.

There were five serious adverse events, including four that were deemed not related to vaccination: hypotension, bilateral nephrolithiasis, legionella pneumonia, and one case of worsening of multiple sclerosis. The vaccine-related serious adverse event was a fever that led to hospitalization because of suspicion of COVID-19. The patient recovered within 12 hours. (Source: Medscape)

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA