Researchers in China have conducted a phase 1/2 trial demonstrating the safety, tolerability, and immunogenicity of a candidate vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent responsible for the current coronavirus disease 2019 (COVID-19) pandemic.
The randomized, double-blind, placebo-controlled trial showed that the inactivated SARS-CoV-2 vaccine, BBIBP-CorV, was safe and well-tolerated among healthy individuals at all doses tested across two age groups (18 to 59 years and 60 years or older).
As reported in The Lancet Infectious Diseases, a robust humoral immune response was observed in all vaccine recipients.
The trial conducted by Xiaoming Yang (Beijing Institute of Biological Products) and colleagues from various other institutions in China was carried out at the Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan Province.
Yang and colleagues report that only mild adverse reactions were observed, with no severe adverse reactions reported across either age group.
“This is the first report of an inactivated SARS-CoV-2 vaccine tested on human participants,” say the researchers. “There is potential for further investigation of this inactivated vaccine for the control and prevention of COVID-19.”
Accelerated efforts to test vaccine candidates
Since the first cases of SARS-CoV-2 were first identified in Wuhan, China, late last year, the virus has now infected more than 39.8 million people and caused more than 1.1 million deaths.
People aged 60 years and older and those with underlying health conditions are at an exceptionally high risk of severe disease and death following infection.
In the absence of any licensed vaccine to protect against SARS-CoV-2, the ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates, say Yang and colleagues.
Testing the inactivated SARS-CoV-2 vaccine candidate BBIBP-CorV
The team has conducted a dose-escalation, randomized, double-blind, placebo-controlled, phase 1/2 trial to assess the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine candidate, BBIBP-CorV, in humans.
Eligible participants were healthy individuals aged 18–80 who tested negative for serum-specific immunoglobulin M (IgM) and IgG antibodies against SARS-CoV-2 prior to enrollment.
For phase 1 of the trial, 192 participants (mean age 53.7 years) were separated into two age groups (18 to 59 years and 60 years or older) before being randomly assigned to receive the BBIBP-CorV vaccine or placebo in a two-dose schedule at 2 μg, 4 μg, or 8 μg on days 0 and 28 via intramuscular injection into the arm.
For phase 2, participants aged 18 to 59 years (mean age 41·7 years) were randomly assigned to receive an intramuscular injection of 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.
The team reports that the BBIBP-CorV vaccine, given as a two-dose immunization, was safe and well-tolerated at all three doses across both age groups. A robust humoral immune response was observed among all vaccine recipients.
The phase 1 findings
During phase 1, at least one adverse reaction occurred within the first 7 days among 42 of 144 individuals who received the vaccine. The most common adverse systemic reaction was fever.
Among those aged 18 to 59, fever developed in one person from the 2μg group, one from the 4μg group, and two from the 8μg group.
Among those aged 60 or older, fever developed in one person from the 8 μg group.
All adverse reactions were mild or moderate in severity, with no serious adverse events reported within 28 days following vaccination.
Across both age groups, neutralizing antibody titers were higher at day 42 among the vaccine recipients than among the placebo recipients.
The phase 2 findings
During phase 2, at least one adverse reaction occurred within the first 7 days among 76 of 336 people who received the vaccine.
At least one adverse reaction occurred in 33 of those who received 8 μg at day 0; 18 who received 4μg at days 0 and 14; 15 who received 4μg at days 0 and 21; and ten who received 4μg at days 0 and 28.
One placebo recipient who received 4μg at days 0 and 21 reported grade 3 fever, but this was self-limiting, and the participant recovered.
All other adverse reactions were mild or moderate in severity. The most common systemic reaction was fever, which developed in one person who received 8μg at day 0; one who received 4μg at days 0 and 14; three who received 4μg at days 0 and 21 and two who received 4μg at days 0 and 28.
The vaccine-elicited neutralizing antibody titers on day 28 were significantly greater among those who received 4μg at day 0 and then again on day 14, 21, or 28 than among those who received just the single 8μg at day 0.
The potential of this vaccine
Yang and colleagues say the trial has shown that the BBIBP-CorV vaccine was safe, tolerable, and immunogenic among healthy adults, whether they were younger than 60 or aged 60 plus.
“Immunization with BBIBP-CorV results in rapid induction of immune responses against SARS-CoV-2, and would be valuable in preventing or limiting the COVID-19 pandemic,” they write.
“Further clinical studies are warranted to evaluate the potential of this vaccine in clinical application,” concludes the team.