Discussion
RBD, headache, pain
ADVERSE REACTIONS, SECONDARY, ADENOVIRUS
In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial including 500 adult participants aged 18–85 years (mean age: 41.2 years), the immunogenicity, efficacy and safety of the Ad5-nCoV COVID-19 vaccine was assessed up to 6 months after vaccination. Both study groups (Ad5-nCoV and Placebo) had similar baseline characteristics. A single immunisation with the Ad5-nCoV vaccine led to a marked immune response. The primary endpoint (seroconversion rate of anti-RBD antibodies on Day 28 after vaccination) and all secondary endpoints on Day 28 after vaccination showed a strong immunogenic response to the Ad5-nCoV vaccine.The Ad5-nCoV vaccine has a good safety profile comparable with the findings of preceding clinical trials in healthy adults. Most post-vaccination AEs were mild or moderate in severity. Although the proportions of participants who reported adverse reactions such as an increase in body temperature, headache, and pain at the injection site were higher in those that received the Ad5-nCoV vaccine, adverse reactions within 28 days were generally mild to moderate and the majority resolved within 7 days after vaccination. All Grade 3 AEs occurred among participants from the Ad5-nCoV group and were similar to commonly reported AEs after other types of immunisation.For those vaccinated with Ad5-nCoV, the seroconversion rate of antibodies against RBD (78.5%) and of NAbs (59.0%) on Day 28 (Interestingly, GMTs of anti-RBD, S protein-specific antibodies and neutralizing SARS-CoV-2 antibodies were elevated at Month 6 post-vaccination in the Placebo group, not by Day 14 or Day 28 (Even disregarding other COVID-19 candidate vaccines that use a recombinant Ad5 vector, adenovirus exposure itself is common. Pre-existing anti-Ad5 immunity may affect the immunogenicity of Ad5-based vaccines, and as a result, their efficacy against COVID-19. However, the proportion of individuals with high anti-Ad5 titres can vary across geographical regions [In this study, we also uncovered the response of pre-existing immunity to Ad5 and showed how it affects subsequent humoral immune responses as well as the longevity of immunity to COVID-19. In participants vaccinated with Ad5-nCoV, there was no difference in humoral immunity to SARS-CoV-2 between those with pre-existing anti-Ad5 titres at baseline above or below the cut-off of 1:200. However using a cut-off of 1:5, we showed that those with pre-existing low Ad5 titres (1:5; Our study provides data on the incidence of anti-Ad5 immunity in the Russian population, admittedly in a relatively small, sample size. Almost all participants had pre-existing neutralising antibodies to Ad5, although levels were generally very low. No such data were available before this study, and only limited and highly variable data are available for the level of Ad5 immunity in Europe.There are currently multiple recombinant Ad-vectored COVID-19 candidate vaccines registered or in development [Other study limitations included the fact all participants were white, although conversely, this also provided the first data in a non-Chinese, European population. Nor did this trial include children or pregnant women, and there were only a small number of older adults (35 were ≥60 years in the Ad5-nCoV group). An ideal candidate vaccine for COVID-19 should cover vulnerable populations of all ages. Anti-S protein-specific antibodies have been reported to decline rapidly in individuals who have recovered from COVID-19, especially those who were asymptomatic or had mild symptoms [