Phase-2 trial using a single dose of recombinant adenovirus vaccine (Ad5-nCoV) vector carries the genetic material that codes for spike glycoprotein of novel coronavirus was found to be safe, well-tolerated, and able to generate rapid immune responses within 14 days and significant humoral and cellular immune responses within 28 days.
Phase-2 trial using a single dose of a vaccine (Ad5-nCoV) that uses a recombinant adenovirus type-5 vector that carries the genetic material that codes for spike glycoprotein of novel coronavirus was found to be safe, well-tolerated, and able to generate rapid immune responses within 14 days and significant humoral and cellular immune responses within 28 days. The adenovirus is a weakened common cold virus.
Besides studying the safety and immunogenicity of the vaccine, the main aim of the trial was to determine the appropriate dose of the candidate vaccine. The Phase-2 trial was carried out in a single centre in Wuhan, China. Healthy adults aged 18 years or older were recruited for the trial. The results were published on July 20 in The Lancet.
While Phase-1 trial did not involve randomisation of participants and did not have a control arm, the Phase-2 trial randomly assigned 508 participants to receive either the vaccine or a placebo. Neither the participants not those conducting the trial know who received the vaccine and who did not.
Two different doses — 1×10¹¹ viral particles and 5×10¹⁰ viral particles — were tested vaccine. The dose with 1×10¹¹ viral particles was given to 253 participants, while the dose with 5×10¹⁰ viral particles was given to 129 participants. The placebo arm had 126 participants.
The vaccine did not cause any serious adverse events within 28 days.. The most common systemic adverse event in both doses was fatigue. Fever and headache were the other two systemic adverse events reported.
Most adverse reactions reported were either mild or moderate. “But 24 (9%) of 253 participants receiving the vaccine at 1×10¹¹ viral particles had severe (grade 3) adverse reaction, which is fever,” they write. This was significantly higher than those receiving the vaccine at 5×10¹⁰ viral particles or placebo. But the grade 3 severe adverse event was self-limiting and resolved within 72-96 hours without any medication.
Both doses produced RBD-specific ELISA antibodies. The seroconversion rates for doses 1×10¹¹ and 5×10¹⁰ were 96% and 97%, respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live coronavirus.
“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 immunisation,” they write.
To assess the efficacy of the vaccine in people who are old, the trial removed the age cap for the recruitment of participants. This allowed inclusion of 65 (13%) participants who were older than 55 years. This was done as older people with chronic diseases are at elevated risk of serious illness and even death. The mean age of the participants was 39·7 years, with 309 (61%) individuals aged 18-44 years, 134 (26%) aged 45-54 years.
Unlike younger participants, older participants had a “significantly lower immune response”, particularly in terms of neutralising antibodies but they showed higher tolerability to the 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,” they write.
Among the 508 participants, 266 (52%) had high pre-existing immunity and 242 (48%) had low pre-existing immunity to the adenovirus type-5 vector used. They found that those with low pre-existing immunity to the adenovirus type-5 vector had two-time higher RBD-specific antibody and neutralising antibody levels compared with those who had high pre-existing immunity to the adenovirus type-5 vector.
“We are planning an international multicentre, randomised, doubleblind, controlled phase 3 effectiveness trial to further evaluate the efficacy of the vaccine,” they say.