Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial

Abstract

BACKGROUND The top priority for the control of COVID-19 pandemic currently is the development of a vaccine. A phase 2 trial conducted to further evaluate the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine (CoronaVac). METHODS We conducted a randomized, double-blind, placebo-controlled trial to evaluate the optimal dose, immunogenicity and safety of the CoronaVac. A total of 600 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine at a dose of 3 μg/0.5 mL or 6 μg /0.5mL, or placebo on Day 0,14 schedule or Day 0,28 schedule. For safety evaluation, solicited and unsolicited adverse events were collected after each vaccination within 7 days and 28 days, respectively. Blood samples were taken for antibody assay. RESULTS CoronaVac was well tolerated, and no dose-related safety concerns were observed. Most of the adverse reactions fell in the solicited category and were mild in severity. Pain at injection site was the most frequently reported symptoms. No Grade 3 adverse reaction or vaccine related SAEs were reported. CoronaVac showed good immunogenicity with the lower 3 μg dose eliciting 92.4% seroconversion under Day 0,14 schedule and 97.4% under Day 0,28 schedule. 28 days after two-dose vaccination, the Nab levels of individual schedules range from 23.8 to 65.4 among different dosage and vaccination schedules. CONCLUSIONS Favorable safety and immunogenicity of CoronaVac was demonstrated on both schedules and both dosages, which support the conduction of phase 3 trial with optimum schedule/dosage per different scenarios.

SARS-CoV-2 vaccines in development

“…They can be produced relatively easily, however, their yield might be limited by productivity of virus in cell culture and the requirement for biosafety level 3 (BSL3) production facilities. Examples are Corona-Vac (initially called PiCoVacc), developed by Sinovac Biotech Ltd. in China 34,35 (discussed below) as well as several other candidates developed in China, by Bharat Biotech in India and by the Research Institute for Biological Safety Problems in Kazakhstan. These vaccines are usually administered intramuscular and might be adjuvanted with alum or other adjuvants.…”

“…Sinovac very recently reported results from a randomized, double blinded placebo controlled Phase II trial (NCT04352608) with their inactivated vaccine (Figure 3c) CoronaVac (the name PiCoVacc was used in the manuscript describing the NHP results, Table 1) in 600 healthy adults (18-59 years of age) 35 . They used two doses, 3 ug or 6 ug, adjuvanted with aluminium hydroxide in a 2 week or 4 week prime-boost regimen.…”

A systematic review of SARS-CoV-2 vaccine candidates

“…27 The inactivated SARS-CoV-2 vaccine containing aluminum hydroxide developed by Sinovac has entered phase 3 clinical trials, with results from the phase 2 trial demonstrating that two doses of 6 μg/0.5 mL or 3 μg/0.5 mL of the vaccine were well-tolerated and immunogenic in healthy adults (Table 1). 43 Phase 2 trial results of the inactivated SARS-CoV-2 vaccine, constructed by Wuhan Institute of Biological Products and Sinopharm, reported that the geometric mean titers (GMT) of NAbs were 121 and 247 at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, displaying only transient and self-limiting adverse reactions. 44 Viral RNA Fig.…”

Development of SARS-CoV-2 vaccines: challenges, risks, and the way forward

“…The safety profile of the vaccine was excellent and both doses were comparable to placebo1. 100 No grade 3 adverse reactions were reported. The phase-III trials in adults and the elderly are underway.…”