Hybrid Immunity to SARS-CoV-2 from Infection and Vaccination—Evidence Synthesis and Implications for New COVID-19 Vaccines

COVID-19 has taken a severe toll on the global population through infections, hospitalizations, and deaths. Elucidating SARS-CoV-2 infection-derived immunity has led to the development of multiple effective COVID-19 vaccines and their implementation into mass-vaccination programs worldwide. After ~3 years, a substantial proportion of the human population possesses immunity from infection and/or vaccination. With waning immune protection over time against emerging SARS-CoV-2 variants, it is essential to understand the duration of protection, breadth of coverage, and effects on reinfection. This targeted review summarizes available research literature on SARS-CoV-2 infection-derived, vaccination-elicited, and hybrid immunity. Infection-derived immunity has shown 93–100% protection against severe COVID-19 outcomes for up to 8 months, but reinfection is observed with some virus variants. Vaccination elicits high levels of neutralizing antibodies and a breadth of CD4+ and CD8+ T-cell responses. Hybrid immunity enables strong, broad responses, with high-quality memory B cells generated at 5- to 10-fold higher levels, versus infection or vaccination alone and protection against symptomatic disease lasting for 6–8 months. SARS-CoV-2 evolution into more transmissible and immunologically divergent variants has necessitated the updating of COVID-19 vaccines. To ensure continued protection against SARS-CoV-2 variants, regulators and vaccine technical committees recommend variant-specific or bivalent vaccines