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

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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.

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Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

B Korber, W.M. Fischer, S. Gnanakaran … (2020)

Summary A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.

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Adaptive immunity to SARS-CoV-2 and COVID-19

Alessandro Sette, Shane Crotty (2021)

The adaptive immune system is important for control of most viral infections. The three fundamental components of the adaptive immune system are B cells (the source of antibodies), CD4+ T cells, and CD8+ T cells. The armamentarium of B cells, CD4+ T cells, and CD8+ T cells has differing roles in different viral infections, and in vaccines, and thus it is critical to directly study adaptive immunity to SARS-CoV-2 to understand COVID-19. Knowledge is now available on relationships between antigen-specific immune responses and SARS-CoV-2 infection. While more studies are needed, a picture has begun to emerge that reveals that CD4+ T cells, CD8+ T cells, and neutralizing antibodies all contribute to control of SARS-CoV-2, in both non-hospitalized and hospitalized cases of COVID-19. The specific functions and kinetics of these adaptive immune responses are discussed, as well as their interplay with innate immunity and implications for COVID-19 vaccines and immune memory against re-infection.

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Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil

Nuno Faria, Thomas A. Mellan, Charles A Whittaker … (2021)

Despite an extensive network of primary care availability, Brazil has suffered profoundly during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Using daily data from state health offices, Castro et al. analyzed the pattern of spread of COVID-19 cases and deaths in the country from February to October 2020. Clusters of deaths before cases became apparent indicated unmitigated spread. SARS-CoV-2 circulated undetected in Brazil for more than a month as it spread north from S o Paulo. In Manaus, transmission reached unprecedented levels after a momentary respite in mid-2020. Faria et al. tracked the evolution of a new, more aggressive lineage called P.1, which has 17 mutations, including three (K417T, E484K, and N501Y) in the spike protein. After a period of accelerated evolution, this variant emerged in Brazil during November 2020. Coupled with the emergence of P.1, disease spread was accelerated by stark local inequalities and political upheaval, which compromised a prompt federal response. Science , abh1558 and abh2644, this issue p. [Related article:] 821 and p. 815 A variant lineage of SARS-CoV-2 associated with rapid transmission in Manaus, Brazil, evolved in November 2020 with immune escape characteristics. Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.