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To what extent does hybrid immunity protect against SARS-CoV-2 and its variants?

To what extent does hybrid immunity protect against SARS-CoV-2 and its variants?

 


The coronavirus disease 2019 (COVID-19) pandemic has been protracted by the emergence of several variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

These variants often carry escape mutations that render them resistant to antibodies induced by vaccines or previous infections. However, hybrid immunity, the combined immunity conferred by both vaccination and natural infection, has been considered the most effective of all preventive measures.

Research: SARS-CoV-2 Hybrid Immunity: Silver Bullet or Silver Lining? Image Credit: Corona Borealis Studio/Shutterstock.com

study: SARS-CoV-2 hybrid immunity: silver bullet or silver lining? Image Credit: Corona Borealis Studio/Shutterstock.com

new nature review immunology A journal study explores hybrid immunity-induced protection against SARS-CoV-2 variants.

prologue

About 75% of people worldwide may have immunity to SARS-CoV-2.Individuals with hybrid immunity are about 50 times higher Neutralizing antibody (nAb) Titers compared to unvaccinated recovered individuals.

cross-reactivity

Researchers have previously suggested that hybrid immunity can protect against new SARS-CoV-2 variants at higher levels compared to natural infection alone. This is also confirmed by the current author.

The enhanced protection of hybrid immunity is due to the recruitment of new B-cell clones to the memory pool. Clonal expansion of persistent immune cells also contributes to hybrid immunity, which occurs when individuals with a prior history of infection with an ancestral, alpha, beta, or delta variant are also vaccinated.

The result is an increase in the number of memory T and B cells by more than an order of magnitude. Since memory B cells are generated by vaccination, SARS-CoV-2 infection leads to a robust increase in antibody production.

The Omicron variant of SARS-CoV-2 and its substrains contain numerous escape mutations. spike protein, with additional key mutations present in other viral proteins. Breakthrough infections with Omicron variants also lead to broadening of their neutralizing activity against other variants, including ancestral and Delta variants.

This cross-neutralizing activity is absent in unvaccinated individuals subsequently infected with the omicron mutant. These individuals display nAbs against her Omicron BA.1, but titers after breakthrough BA.1 infection are 6-fold higher than hers compared to corresponding anti-Delta nAb titers after breakthrough Delta infection. lower.

In general, the more pathogenic the variant, the higher the nAb titer. However, hybrid immunity with Omicron’s breakthrough infection provides broad cross-protection against multiple variants.

durability

Vaccine-induced and innate immunity to SARS-CoV-2 declines significantly over time, resulting in less protection against reinfection. However, recent reports indicate that the highest level of protection from hybrid immunization is 10-20 confirmed infections per 100,000 person-days of risk.

Hybrid immunization was found to provide superior protection compared to postinfection and double vaccination immunization at 30 and 90 reinfections per 100,000 person-days, respectively. Furthermore, hybrid immunization with only one dose of vaccine before and after natural infection provided immunity equivalent to three doses of vaccine.

One previous study found that hybrid immunity provided 60% protection against both BA.1 and BA.2 variants up to 9 months after infection.

T cell effect

T cells provide the strongest markers of protection against moderate to severe disease. nAbs become less potent and ultimately ineffective against evolving escape variants, but T cells Immunity is preserved because T-cell receptor (TCR) epitopes are not altered between variants.

B cell responses were 10-fold less effective against pre-Omicron variants compared to Omicron, whereas T cell responses showed only a 10-30% reduction.

T cell immunity is not enhanced by vaccination after natural infection and vice versa. However, the humoral response appears to be enhanced by these events. His T-cell response to Omicron infection in hybrid immunity was ancestral or alpha-His variant infected if a second exposure (whether by vaccination or reinfection) occurred during the Omicron wave It is not boosted by humans. That is, the initial SARS-CoV-2 exposure triggers the imprinting of her T cells that determines the development of future hybrid immunity.

Our goal

Hybrid immunity may provide strong protection against symptomatic infection when the antigens of the infectious variant have a phenotype similar to that of the early priming variant. A new vaccine containing the Omicron spike protein failed to provide the same level of protection against this strain.

Researchers are proposing to broaden the scope of immunological testing and vaccination. If cross-reactive antibody titers are increased by vaccine boosters, these should contain conserved regions of viral non-spiking genomic ribonucleic acid (RNA) from different SARS-CoV-2 variants. Mucosal immunity should be induced along with systemic immunity by mucosal vaccination.

This vaccination approach is especially useful for people with hybrid immunity. Because mucosal vaccines boost resident immune cells already primed by SARS-CoV-2 during previous challenges.

Hybrid immunity may not be the silver bullet to end the SARS-CoV-2 pandemic, but it is a silver lining that we can learn to move to the next level of vaccine design and delivery.

Journal reference:

  • Suryawanshi, R. & Ott, M. (2022). SARS-CoV-2 hybrid immunity: silver bullet or silver lining? nature review immunology. doi:10.1038/s41577-022-00771-8.

Sources

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