Randomized Controlled Trial
Study population and setting
This study presents an interim analysis of the safety and immunogenicity findings from two ongoing clinical trials (a phase 1 and a phase 2) in Henan Province, China evaluating the Sinopharm COVID-19 vaccine, which consists of β-propiolactone inactivated SARS-CoV-2 with an alum adjuvant. In the phase 1 trial, 96 participants were randomized and equally distributed to three vaccine dose groups (low, medium, high; with injections on days 0, 28, and 56) or an alum-only control group. In the phase 2 trial, 112 participants were randomized to two vaccine dose schedules (injections on days 0 and 14 ,or on days 0 and 28) using the medium dose from the phase 1 trial, with alum-only controls in a 1:3 ratio with vaccine recipients for each group.
For both trials, safety was assessed by recording adverse reactions for seven days following injection, and immunogenicity was assessed by measuring neutralizing antibody and total specific IgG titers 14 days after the final injection.
Summary of Main Findings
For both trials, adverse reactions were mild, with pain at the injection site as the most common finding, followed by transient fever; none required treatment. The overall incidence rate for adverse reactions was relatively low at 15%, possibly suggesting a superior safety profile compared to other COVID-19 vaccines currently in clinical trials.
Seroconversion rates were generally very high (most groups were 100%, with the lowest at 87.5%) for both neutralizing antibodies and total specific IgG. Booster injections given after a longer interval (21 or 28 days vs. 14 days) following the prime injection produced higher neutralizing antibody and total specific IgG titers.
Evidence from these clinical trials, and from preclinical studies in rhesus macaques, suggests that this inactivated vaccine is not associated with antibody-dependent enhancement (ADE) or vaccine-associated enhanced respiratory disease (VAERD), although further study is required to more definitively address these important safety concerns.
The studies are well-designed double-blind, placebo-controlled, randomized clinical trials assessing both different doses and dose schedules for safety and immunogenicity. This combined interim analysis of both phase 1 and 2 trials together provides useful data that have been utilized to aid the design of phase 3 trials with this vaccine, which are now underway.
This study is an unplanned interim analysis of ongoing clinical trials, and the authors stress that cautious interpretation is warranted as thorough analysis of the full dataset, when available, will be crucial for validation of these preliminary findings.
Although emerging evidence suggests neutralizing antibodies play an important role in immunity against SARS-CoV-2, the correlates of protection for COVID-19 remain poorly defined to date, and this study reports only humoral immune response data. Furthermore, methods for quantifying antibodies against SARS-CoV-2 are not yet broadly standardized, thus comparison between studies is difficult.
No possible explanation was provided for the greater seroconversion rate for neutralizing antibodies (41/42 participants) vs. total specific IgG (36/42 participants) for the 0- and 14-day group in the phase 2 trial.
This is the first clinical trial data reported for an inactivated SARS-CoV-2 vaccine against COVID-19.
This review was posted on: 27 August 2020