V9* China Immunogenicity and Safety of a Recombinant Adenovirus Type-5-Vectored COVID-19 Vaccine in Healthy Adults aged 18 years or Older

Ad5-vectored COVID-19 Vaccine Confirmed Effective 

Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The primary endpoints for immunogenicity were the geometric mean titers (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralizing antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. 

603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020

Randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). 

In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2–749·2) and 571·0 (467·6–697·3), with seroconversion rates at 96% (95% CI 93–98) and 97% (92–99), respectively, at day 28. 

Both doses of the vaccine induced significant neutralizing antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8–22·7) and 18·3 (14·4–23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles.

Specific interferon γ enzyme-linked immuno-spot assay responses post vaccination were observed in 227 (90%, 95% CI 85–93) of 253 and 113 (88%, 81–92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. 

No serious adverse reactions were documented.

Interpretation

The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunization.
This study provides more evidence for the immunogenicity and safety of the Ad5-vectored COVID-19 vaccine in a larger population.

Results suggest a single-dose immunization schedule of Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is an appropriate regimen for healthy adults. 

Compared with the younger population, we found older people to have a significantly lower immune response, but higher tolerability, to the Ad5-vectored COVID-19 vaccine. 
Therefore, an additional dose might be needed to induce a better immune response in the older population, and this will be evaluated in a phase 2b trial.

The detection limits for the neutralizing antibody tests to live SARS-CoV-2 virus and a pseudo-virus were 1:8 and 1:10.

At day 28, the RBD-specific ELISA antibodies peaked at 656·5 (575·2–749·2) in the 1 × 1011 viral particles dose group and 571·0 (467·6–697·3) in the 5 × 1010 viral particles dose group. 244 (96%, 95% CI 93–98) of 253 participants in the 1 × 1011 viral particles dose group and 125 (97%, 92–99) of 129 participants in the 5 × 1010 viral particles dose group showed seroconversion of RBD-specific ELISA antibodies at day 28, whereas the participants in the placebo group showed no antibody increase from baseline.

Age and pre-existing anti-Ad5 immunity of the participants could have affected the candidate vaccine's safety and immunogenicity.

One injection of the vaccine might be inadequate to induce a high level of humoral immune responses, particularly for people aged 55 years or older.

Both neutralizing antibody and T-cell responses were important in eliminating the virus and controlling disease development in patients with COVID-19 who were naturally infected by SARS-CoV-2.

COVID-19 appears to have a more benign course in children, with almost no fatalities reported.

The baseline anti-Ad5 immunity of the participants seemed to be representative of Chinese adults, according to the previously reported studies;
 however, anti-Ad5 immunity in adults varies from place to place globally, with reported proportions of adults with neutralizing antibodies titers for Ad5 of more than 1:200 of about 80% in India, 78% in Kenya, 67% in Thailand, 64% in Uganda, around 60% in South Africa, 45% in Sierra Leone, and less than 30% in the USA.
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Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial - The Lancet

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