SARS-CoV-2 vaccine safely induces an immune response in healthy volunteers

Preliminary data from the Phase I/II trial testing the safety of the BBIBP-CorV vaccine, based on an inactivated whole SARS-CoV-2 virus, suggested the vaccine candidate is safe and can elicit an antibody response.

The study included participants aged 18 to 80 years old, all of which had antibody responses. Participants aged 60 plus were slower to respond, taking 42 days before antibodies were detected in all recipients, compared with 28 days for participants aged 18-59. Antibody levels were also lower in those aged 60-80 years compared to the younger participants (Mean neutralising antibody titre 42 days after receiving a 8μg vaccine dose was 228.7 for people aged 18-59 and 170.9 for those aged 60-80).

The trial was not designed to assess vaccine efficacy, so the investigators cannot comment on whether the antibody responses induced by BBIBP-CorV are sufficient to protect from SARS-CoV-2 infection.

Professor Xiaoming Yang, one of the authors of the study, from the Beijing Institute of Biological Products Company Limited, China, said: “Protecting older people is a key aim of a successful COVID-19 vaccine as this age group is at greater risk of severe illness from the disease. However, vaccines are sometimes less effective in this group because the immune system weakens with age. It is therefore encouraging to see that BBIBP-CorV induces antibody responses in people aged 60 and older, and we believe this justifies further investigation.”

Currently, 42 potential COVID-19 vaccines are undergoing clinical trials. There is a huge variety in type, ranging from DNA plasmid vaccines to inactivated virus vaccines, adenovirus-vectored vaccines to RNA vaccines, protein subunit vaccines and virus-like particle vaccines. Some of these have already been shown to be safe and to elicit immune responses in early clinical trials.

The BBIBP-CorV vaccine includes an inactivated SARS-CoV-2 virus that was isolated from a patient in China and grown in the lab using cell lines. The virus is inactivated using a chemical called beta-proprionolactone for inclusion in the vaccine. BBIBP-CorV also includes an aluminium hydroxide adjuvant, which boosts immune responses.

The first phase of the study was designed to find the optimal safe dose for BBIBP-CorV. It involved 96 healthy volunteers aged between 18 and 59 years and a second group of 96 participants aged between 60 years and 80 years. Within each group, the vaccine was tested at three different dose levels (2μg, 4μg and 8μg, 24 participants per group), with two vaccinations administered on day zero and day 28. A fourth group within each age range (24 participants in each age group) were given two doses of a placebo vaccine. A total of 144 participants received the vaccine and 48 received the placebo in Phase I of the study.

The second phase of the study was designed to identify the optimal timing schedule for vaccination. A total of 448 participants aged between 18 and 59 years were randomly assigned to receive either one 8μg shot of vaccine or placebo; or two shots of 4μg vaccine or placebo at zero and 14 days, zero and 21 days or zero and 28 days. In this second phase, there were 112 participants per group, with 336 receiving the vaccine and 112 receiving the placebo.

Participants were asked to report any adverse events for the first seven days after each vaccination and these were verified by the research team. Thereafter, participants recorded any adverse events using paper cards for the following four weeks. During Phase I, laboratory tests were carried out after the vaccinations to assess kidney, liver and other organ functions. Blood samples were taken to test antibody levels for SARS-CoV-2 before and after vaccination.

No serious adverse events were reported within 28 days of the final vaccination. The most common side effect was pain at the injection site of vaccine recipients. A small number of participants reported experiencing a fever. There were no instances of clinically significant changes in organ functions detected in laboratory tests in any of the groups.

The greatest antibody responses were elicited by two 4μg doses of the vaccine at either zero and 21 days or zero and 28 days (mean neutralising antibody titres 28 days after second vaccination were 282.7 for two 4μg injections at day zero and 21; and 218.0 for two 4μg injections at day zero and 28).

Professor Xiaoming Yang said: “Our findings indicate that a booster shot is necessary to achieve the greatest antibody responses against SARS-CoV-2 and could be important for protection. This provides useful information for a Phase III trial.”

The authors noted some limitations with the study, including the short duration of follow up at just 42 days. They also highlighted that the study did not include children and adolescents aged under 18. Trials with these groups will be carried out when the full analysis of data from adult groups is completed, the researchers say.

The findings were published in The Lancet Infectious Diseases.