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Review
. 2023 Jan 27;11(2):370.
doi: 10.3390/biomedicines11020370.

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

Julia R Spinardi  1 , Amit Srivastava  2
Affiliations
Review

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

Julia R Spinardi et al. Biomedicines. .

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; booster; breakthrough infection; hybrid immunity; infection; mRNA vaccine; reinfection; transmission; vaccination.

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Conflict of interest statement

Julia Spinardi is a Pfizer employee and may hold stock options. Amit Srivastava is currently employed by Orbital Therapeutics; he was a Pfizer employee at the time of manuscript development and may hold stock options.

Figures

Figure 1
Figure 1
The challenges of maintaining protection against SARS-CoV-2 [10,11,12,13,14,15,16,17,18].
Figure 2
Figure 2
Evidence synthesis approach/strategy. The gray triangle symbolizes three types of immune protection, namely that obtained through vaccination, infection, or a combination of both. Accumulating data have enhanced our understanding of the Nature of Protection conferred by the three types of immunity against various COVID-19 outcomes.
Figure 3
Figure 3
Lessons learned from widespread infection and vaccination. VOC, variants of concern.
See this image and copyright information in PMC

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