Johnson & Johnson’s COVID-19 Vaccine Phase 1/2a Trial Results

Johnson & Johnson’s coronavirus disease 2019 (COVID-19) vaccine, Ad26.COV2.S, showed robust T-cell, according to findings from an interim analysis published in The New England Journal of Medicine.

In this multicenter, placebo-controlled, phase 1/2a trial, participants were recruited at 12 sites in Belgium and the United States. Cohort 1a and 1b (n=402) included adults aged 18 to 55, and cohort 3 (n=403) included adults aged 65 and older. Cohort 2 was initiated to collect longer-term data comparing a single-dose regimen with a 2-dose regimen, but data from this cohort is not reported in this study.

Participants received Ad26.COV2.S at either high dose (HD) or low dose (LD) intramuscularly 56 days apart. Invesigators randomized patients in cohorts 1 and 3 in a 1:1:1:1:1 ratio to receive either LD+LD, LD+placebo, HD+HD, HD+placebo, or placebo+placebo. Results collected after the second dose in cohort 1a and after the first dose in cohort 3 are reported. Reactogenicity, immunogenicity, and safety were evaluated after 7, 28, and 71 days.

Cohort 1

By day 29, participants experienced seroconversion greater than 99% among the all groups except in participants who received 2 doses of placebo. The raw geometric mean concentration (GMC) of antibodies against the SARS-CoV-2-specific spike protein increased through day 57 and remained consistent through day 71.

At day 15, CD8+ T-cell response to S peptides were detected in 51% and 64% of participants, Th1 response to S peptides were detected in 76% and 83% of participants, and CD4+ Th1 response to S peptides were 0.08% and 0.11% among the low- and high-dose groups, respectively.

Injection site pain was reported in 78% of high-dose recipients, 64% of low-dose recipients, and 9% of placebo recipients.

Cohort 3

By day 15 in cohort 3, seroconversion was greater than 75% among vaccine recipients, which increased to 96% among the high-dose group by day 29. GMC levels were lower among cohort 3 relative to cohort 1 at day 29.

At day 15, CD8+ T-cell response to S peptides were detected in 36% and 24% of participants, Th1 response to S peptides were detected in 60% and 67% of participants, and CD4+ Th1 response to S peptides were 0.09% and 0.11% among the low- and high-dose groups, respectively.

Injection site pain was reported in 42% of high-dose recipients, 41% of low-dose recipients, and 14% of placebo recipients.

Overall, grade 3 systemic events were highest among participants aged 31 to 45 years receiving a low dose (43%), followed by participants aged 18 to 30 receiving high dose (26%). All other groups reported less than 25% grade 3 systemic events.

A total of 5 serious adverse events were, but only the high fever was attributed to vaccination. No participant discontinued the trial due to an adverse event.

These phase 1/2a trials were limited by the lack of ethnic diversity.

This interim analysis of the Ad26.COV2.S vaccine suggested a safe and acceptable reactogenicity profile. Participants were immunogenic after a single vaccination with either the low or high dose.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Sadoff J, Le Gars M, Shukarev G, et al. Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine. [published online January 13, 2021] N Engl J Med. doi:10.1056/NEJMoa2034201.