An investigational inactivated whole-virus coronavirus disease 2019 (COVID-19) vaccine has demonstrated safety and immunogenicity, according to the results of an interim analysis published in JAMA.
The study authors examined safety outcomes 28 days, and immunogenicity outcomes 14 days after 3 doses in a phase 1 trial and 2 doses in a phase 2 trial of an inactivated COVID-19 vaccine candidate (WIV04 strain, National Genomic Data Center of the Chinese Academy of Science accession No. SAMC133237, and GenBank accession number MN996528,) in healthy adults in China.
The double-blind, randomized, placebo-controlled study (Chinese Clinical Trial Registry Identifier: ChiCTR2000031809) was designed by the Wuhan Institute of Biological Products Co Ltd, and Henan Provincial Center for Disease Control and Prevention (CDC). Healthy adults aged 18 to 59 years without a history of severe acute respiratory syndrome coronavirus (SARS-CoV) or SARS-CoV-2 infection were eligible for enrollment.
Currently, there are 160 COVID-19 candidate vaccines in various stages of development, with 25 in different phases of clinical trials. This is the first report of phase 1 and 2 clinical trials of a whole virus-inactivated COVID-19 vaccine in adults. In the phase 1 trial, 96 participants were assigned to 1 of 3 dose groups (2.5, 5, and 10 µg) and an aluminum hydroxide (alum) adjuvant-only group (n=24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomly assigned to 5 µg doses in 2 schedule groups (injections on days 0 and 14 [n=84] vs alum only [n=28], and days 0 and 21 [n=84] vs alum only [n=28]). The vaccine was well tolerated in all dose groups under different injection procedures with no serious adverse events.
The antibody response was monitored over 14 days after injections, and results suggested that the inactivated vaccine may effectively induce antibody production. However, it is unclear whether vaccine induced antibody levels could persist and could affect susceptibility and pathogenesis of SARS-CoV-2 infection. The participants are scheduled to be followed up to 1 year and a phase 3 trial has been initiated.
There were several study limitations, including the fact that the interim analysis was not prespecified in the original protocol and was added during the study to provide information for the design of a phase 3 trial. Also, the current analysis reported results from only some groups, which means the study was potentially underpowered for comparison of adverse events. Therefore, a full analysis of the entire trial population is needed to understand the profile of the inactivated vaccine regarding tolerability, immunogenicity, and immune persistence.
“In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse events assessment will require phase 3 trials,” concluded the authors.
Disclosure: This clinical trial was supported by Wuhan Institute of Biological Products Co Ltd. Please see the original reference for a full list of authors’ disclosures.
Xia S, Duan K, Zhang Y, et al. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: interim analysis of 2 randomized clinical trials. JAMA. Published online August 13, 2020. doi:10.1001/jama.2020.15543