Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial

Abstract

Background The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates. We aimed to assess the safety and immunogenicity of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate, BBIBP-CorV, in humans.Methods We did a randomised, double-blind, placebo-controlled, phase 1/2 trial at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan Province, China. In phase 1, healthy people aged 18-80 years, who were negative for serum-specific IgM/IgG antibodies against SARS-CoV-2 at the time of screening, were separated into two age groups (18-59 years and ≥60 years) and randomly assigned to receive vaccine or placebo in a two-dose schedule of 2 μg, 4 μg, or 8 μg on days 0 and 28. In phase 2, healthy adults (aged 18-59 years) were randomly assigned (1:1:1:1) to receive vaccine or placebo on a single-dose schedule of 8 μg on day 0 or on a two-dose schedule of 4 μg on days 0 and 14, 0 and 21, or 0 and 28. Participants within each cohort were randomly assigned by stratified block randomisation (block size eight) and allocated (3:1) to receive vaccine or placebo. Group allocation was concealed from participants, investigators, and outcome assessors. The primary outcomes were safety and tolerability. The secondary outcome was immunogenicity, assessed as the neutralising antibody responses against infectious SARS-CoV-2. This study is registered with www.chictr.org.cn, ChiCTR2000032459. FindingsIn phase 1, 192 participants were enrolled (mean age 53•7 years [SD 15•6]) and were randomly assigned to receive vaccine (2 μg [n=24], 4 μg [n=24], or 8 μg [n=24] for both age groups [18-59 years and ≥60 years]) or placebo (n=24). At least one adverse reaction was reported within the first 7 days of inoculation in 42 (29%) of 144 vaccine recipients. The most common systematic adverse reaction was fever (18-59 years, one [4%] in the 2 μg group, one [4%] in the 4 μg group, and two [8%] in the 8 μg group; ≥60 years, one [4%] in the 8 μg group). All adverse reactions were mild or moderate in severity. No serious adverse event was reported within 28 days post vaccination. Neutralising antibody geometric mean titres were higher at day 42 in the group aged 18-59 years (87•7 [95% CI 64•9-118•6], 2 µg group; 211•2 [158•9-280•6], 4 µg group; and 228•7 [186•1-281•1], 8 µg group) and the group aged 60 years and older (80•7 [65•4-99•6], 2 μg group; 131•5 [108•2-159•7], 4 μg group; and 170•87 [133•0-219•5], 8 μg group) compared with the placebo group (2•0 [2•0-2•0]). In phase 2, 448 participants were enrolled (mean age 41•7 years [SD 9•9]) and were randomly assigned to receive the vaccine (8 μg on day 0 [n=84] or 4 μg on days 0 and 14 [n=84], days 0 and 21 [n=84], or days 0 and 28 [n=84]) or placebo on the same schedules (n=112). At least one adverse reaction within the first 7 days was reported in 76 (23%) of 336 vaccine recipients (33 [39%], 8 μg day 0; 18 [21%], 4 μg days 0 and 14; 15 [18%], 4 μg days 0 and 21; and ten [12%], 4 μg days 0 and 28). One placeb...

A Comprehensive Summary of the Knowledge on COVID-19 Treatment

“…Inactivated and subunit vaccines are virus-based vaccines made from the killed virus or the fragment of the virus. In China, two inactivated vaccines BBIBP-CorV [ 161 ] and CoronaVac [ 160 ] developed by Sinopharm and Sinovac Biotech, respectively, are already in clinical Phase III. Adenovirus vector, lentiviral vector, and measles virus vector vaccines are viral vector-based vaccines divided into two types according to the technology: replicating viral vector and nonreplicating viral vector vaccines.…”

Influenza Vaccination Quality Improvement as a Model for COVID-19 Prophylaxis

“…The most salient unknown is the rapidly evolving knowledge base and research for the SARS-CoV-2 virus. Compared to the decades of research that exists for influenza and other pathogens in the modern vaccination schedule, the COVID-19 vaccine has limited studies and an expedited timeline for safety and quality review [ 30 ]. Even the mechanism of action for the proposed vaccine is novel in using a messenger ribonucleic acid to produce an antigenic response instead of traditional viral proteins [ 8 , 9 ].…”

SARS-CoV-2 vaccines in advanced clinical trials: Where do we stand?

“…The surface glycoprotein S is responsible for binding to the major host receptor for SARS-CoV-2, angiotensin converting enzyme 2 (ACE2), and for mediating fusion between the viral and host cell membranes. This makes S protein the principal target of neutralizing antibody responses [ [41] , [42] , [43] ] which are so far the best described correlate of protection against infection in humans [ [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] ], and in animal challenge studies [ 45 , [53] , [54] , [55] , [56] , [57] ]. The SARS-CoV-2S is a class I homotrimeric transmembrane protein that is expressed on the surface of the viral particle and exists in a prefusion metastable conformation.…”

“…All adverse reactions (ARs) were mild or moderate in severity with 29% of vaccine recipients reporting at least one AR within the first 7 days of vaccination. No serious adverse events (AEs) were reported within the 28 days after vaccination [ 47 ].…”