Efficacy and immune responses of COVID-19 vaccines
The RBD of the SARS-CoV-2 spike protein is the primary target for neutralizing antibodies induced by COVID-19 vaccines. Specific IgG antibodies against conformational but not sequential RBD epitopes have the potential to block the binding of SARS-CoV-2 with ACE2 and confer protective immunity179. Mutations in RBD, as identified in several VOC, display increased binding affinity to ACE2180 and/or reduced neutralization ability of sera from convalescent and BNT162B2 vaccinated individuals181-184. Noticeably, BNT162b2-induced IgG antibodies had higher avidity to mutated RBD than those induced by natural infection66. The variant Omicron exhibited approximately fourfold greater immune escape relative to the Beta variant183. Prior COVID-19 was associated with higher neutralization capacity for the ancestral virus after BNT162b2 vaccination183. More importantly, two doses of mRNA COVID-19 vaccines provided almost non-existent, whereas a booster dose yielded almost 75% protection against symptomatic infection of Omicron184. It is predicted that BNT162b2 boosted, or vaccination (two doses) combined with previous infection can prevent 73% symptomatic infection by Omicron, which is significantly higher than in individuals with BNT162b2 vaccination only183.
Other types of vaccines have also been administered around the world. CVnCoV is a vaccine based on unmodified RNA and induced only a 48% reduction in the incidence of symptomatic disease185. CV2CoV is the second-generation unmodified mRNA vaccine but with optimized non-coding regions and enhanced antigen expression. Compared to CVnCoV, CV2CoV induced higher titers of binding and neutralizing antibodies against SARS-COV-2 variants, and memory B and T cell responses non-human primates186. The inactivated Sinopharm/BBIBP COVID-19 vaccine is widely used in developing countries including China due to its low storage requirements. Seroconversion rates in unexposed individuals after first and second dose reached 40% and 100% respectively, and younger individuals and women had the highest antibody concentrations. Previous SARS-CoV-2 infection was associated with a strong antibody response after a single dose of the BBIBP vaccine. A sharp increase in antibody concentrations was observed following SARS-CoV-2 infection after the first and second doses187. Virus-like particle-based COVID-19 vaccines induced high levels of neutralizing antibodies and protection against infection with SARS-CoV-2 and its variants in mice and rhesus macaques188,189. PreS-RBD vaccine was developed based on a recombinant fusion protein consisting of the human hepatitis B virus-derived PreS antigen and two SARS-CoV-2 RBD domains. It induced a robust anti-RBD IgG response in rabbits consisting of an early IgG1 and sustained IgG4 which can be detected in serum and mucosa secretions. Moreover, the vaccine-induced antibodies potently inhibited the interaction of RBD with ACE2 and possessed the neutralizing ability of the omicron VOC190. The efficacy and immune responses elicited by different types of COVID-19 vaccines are listed in Table 3.