Analysis supports phase 3 trials of Johnson & Johnson’s COVID-19 vaccine

Researchers in the Netherlands, the United States, and Belgium have presented early-stage clinical trial results demonstrating the safety and efficacy of Johnson & Johnson’s vaccine candidate for coronavirus disease 2019 (COVID-19).

Phase 1–2a interim results show that the vaccine is safe and immunogenic in both younger and older adults after just a single dose, thereby supporting evaluation in phase 3 trials.

Those trial results are expected by the end of January 2021, at which point Johnson & Johnson hopes to apply for authorization from the US Food and Drug Administration (FDA).

The vaccine is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector that encodes the full-length spike (S) protein found on the surface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes COVID-19. The S protein is the primary surface structure the virus uses to bind to and infect host cells.

Currently called by its experimental name – Ad26.COV2.S – the vaccine is being tested in a multicenter, placebo-controlled, phase 1–2a clinical trial that was initiated on July 22, 2020.

The trial is funded by Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services. Representatives from Johnson & Johnson’s vaccine arm – Janssen – designed and manufactured the vaccine, designed the trial, and conducted the analysis.

What did the study involve?

Healthy adults aged between 18 and 55 (cohort 1) and those aged 65 or older (cohort 3) were randomly assigned to receive the vaccine at a low dose (5×10¹⁰ viral particles [VPs] per mL) or high dose (1×10¹¹ VPs/mL) or placebo either as a single-dose or two-dose regimen (separated by 56 days). Enrollment for cohort 2 was initiated in November 2020 to collect longer-term data comparing a single-dose and two-dose regimen, but it is the interim results for cohorts 1 and 3 that have now been reported.

Hanneke Schuitemaker from Janssen Vaccines and Prevention in Leiden, the Netherlands, and colleagues found that both the one-dose and two-dose regimens elicited effective antibody and T-cell responses against SARS-CoV-2 among all 805 participants.

All participants had neutralizing antibodies by day 57

As reported in the New England Journal of Medicine, neutralizing antibodies were detected in 90% or more of all participants by day 29 following one dose of the vaccine and by day 57, this figure had reached 100%. A second vaccine dose boosted antibody titers by a factor of 2.6 to 2.9.

Furthermore, by day 14, the team had detected CD4+ T-cell responses in 76 to 83% of the participants in cohort 1 and in 60 to 67% of participants in cohort 3. The vaccine also induced robust CD8+ T-cell responses.

Following the first vaccine dose in both cohorts and following the second dose in cohort 1, the most frequently solicited adverse events were fatigue, headache, myalgia, and pain at the injection site.

Local and systemic reactions occurred either on the day of immunization or the following day and generally resolved within 24 hours.

A single-dose vaccine would have obvious advantages

The researchers say that while all ongoing phase 3 studies of other COVID-19 vaccines have assessed two-dose regimens, the findings show that just a single dose of Ad26.COV2.S elicited a robust humoral response in most vaccine recipients, irrespective of dosing size or participants’ age.

“An efficacious single-dose COVID-19 vaccine has obvious logistic advantages over a two-dose vaccine, especially during a pandemic,” writes Schuitemaker and colleagues.

Whether a second dose will provide additional efficacy or durability benefit is currently being studied in one of the phase 3 clinical trials.

Johnson & Johnson said in a statement that it anticipates being able to announce topline phase 3 data for its single-dose Janssen COVID-19 vaccine candidate by late January 2021, although the timing is approximate.

“If the single-dose vaccine is shown to be safe and effective, the company expects to submit an application for Emergency Use Authorization with the U.S. Food and Drug Administration shortly afterwards, with other regulatory applications around the world to be made subsequently,” the company adds.