Randomized Controlled Trial
Study population and setting
This study presents the interim results of a Phase 1/2a randomized, double-blinded, placebo-control clinical trial assessing the safety and immunogenicity of a non-replicating recombinant adenovirus 26-vectored SARS-CoV-2 vaccine (Ad26.COV2.S) expressing full-length, stabilized SARS-CoV-2 S (spike) protein currently in development by Janssen Pharmaceutical/Johnson & Johnson. The study cohorts consisted of adults aged 18-55 and ≥ 65 in the United States and Belgium. Two doses of the vaccine were evaluated, each administered intramuscularly (IM) either as a single dose or as a two-dose regimen (administered on day 0 and day 56), with a control group receiving a saline-only injection. Safety was assessed by monitoring solicited adverse events (AEs) for 7 days, unsolicited AEs for 28 days, and serious adverse events (SAEs) throughout the study. Immunogenicity was assessed by measurement of both humoral and cellular responses.
Summary of Main Findings
AEs were generally limited to pain at the injection site, fatigue, headache, and myalgia. Fever was reported in 19% of participants, with a grade 3 fever present in 5%. One vaccine-related SAE was reported: a fever that required hospitalization due to suspicion of COVID-19. Seroconversion rates for total specific IgG were very high (99-100%) for all groups, and a 4-fold or greater increase in binding antibody titer was achieved for most of the participants that were found to be seropositive prior to vaccination. Seroconversion rates for neutralizing antibodies were also high (83-100%) for all groups. Stimulation of cellular immunity was also generally robust, with 67-100% of participants producing detectable CD4+ responses. Only 1 participant produced a detectable CD4+ Th2 response, and overall was still strongly CD4+ Th1-skewed; thus, concerns for vaccine-associated enhanced respiratory disease (VAERD) were judged to be minor. Detectable CD8+ responses were detected in 33-64% of participants.
This study had a strong design and included the important group aged ≥ 65 years. Both humoral and cellular immune responses are assessed, with attention given to CD4+ Th1/Th2 ratios as necessitated by concern for VAERD.
The data presented are still very preliminary, with many participants/groups currently excluded from the report (e.g. only data from 15 participants from the ≥ 65 year-old group is included). Although seropositivity rates for Ad26 amongst the participants “will be reported later” according to authors, this is an important piece of data to assess the potential for vaccine failure in the context of previous exposure to Ad26. Additionally, the continued lack of standardization in the assays used makes comparison to other vaccines in development difficult.
These preliminary data indicate that the Janssen Pharmaceutical/Johnson & Johnson Ad26.COV2.S SARS-CoV-2 vaccine is generally safe and immunogenic, and remains a viable contender in the ongoing effort to develop an efficacious vaccine against COVID-19.
This review was posted on: 16 November 2020