Previous spike protein exposure forms protection against SARS-CoV-2 omicron mutants

In a recent study published in ChemistryResearchers have found that the immune enhancement by the coronavirus 2 (SARS-CoV-2) omicron variant of severe acute respiratory syndrome depends on the history of previous coronavirus disease 2019 (COVID-19).

The SARS-CoV-2 Omicron mutant, which emerged in late 2021, was highly contagious and quickly replaced the previously predominant mutant. It shows the highest difference from the ancestral Wuhan strain, Spike protein, More than any previous concern (VOC). Various studies have observed that two or three vaccinations prevent severe illness and hospitalization due to Omicron infection.

Evidence suggests that vaccinated people generally have 20-40-fold lower neutralizing titers against Omicron mutants, making them the most antibody-avoidant mutants.In addition, protection against the severe symptoms of vaccinated individuals may be due to partial activity of residues. Neutralizing antibody (NAbs) and primed B and T cells memory.

About research

The current study investigated how infection with SARS-CoV-2 omicrons enhances cross-reactive B and T cell immunity to itself and other VOCs. The authors recruited a cohort of healthcare professionals (HCWs) that were tracked longitudinally from March 2020 to January 2022. These cohorts were individuals with different combinations of vaccination and infection history.

Healthcare professionals can use consecutive COVID-19 waves, ie, from alpha, delta, and omicron, and with the BNT162b2 vaccine partially (first dose), complete (two doses), and booster (third dose). Identified after vaccination. Nucleocapsid (N) and spike 1 (S1) receptor binding domain (RBD) serology were assessed longitudinally. The authors observed that a third exposure to spikes increased S1RBD titers in most healthcare workers 2-3 weeks after the latest vaccination.

In addition, the antibody response peaked with the third vaccination. Triple vaccinated HCW infected with SARS-CoV-2 Wuhan Hu-1 significantly reduced anti-RBD titers against beta, delta, and omicron variants compared to SARS-CoV-2 naive health care workers. I did. In addition, cross-reactive anti-RBD immunoglobulin G (IgG) and nAb to Omicron VOC were significantly reduced compared to other mutants, regardless of infection history.

The frequency of memory B cells (MBCs) for the S proteins of Wuhan Hu-1, Delta, and Omicron mutants was 2-3 weeks after the third vaccination compared to 20-21 weeks after the second vaccination. Increased. The frequency of MBC for S protein in Wuhan Hu-1 and delta mutants was similar regardless of previous infection, but for Omicron S1 2-3 weeks after booster administration and 20-21 weeks after the second administration. Significantly decreased.

Half of the maximum inhibitory concentration of RBD or total S antibody and live virus nAb (IC)₅₀) Correlates for alpha and delta variants, but not for beta, gamma, and omicrons, suggesting that antibody binding was an inadequate marker of nAbIC.₅₀.. Next, we compared T cell responses after 2-3 weeks of booster immunization between healthcare professionals who were SARS-CoV-2 naive or infected with the Wuhan Hu-1, Delta, or Omicron mutant. did.

T cell immunity was compared to a mapped epitope pool (MEP) of Wuhan Hu-1 spike peptide with S1 from Wuhan Hu-1 or S1 protein with delta or omicron mutations. The magnitude of the response of Omicron to S1 was significantly lower. Notably, more than half (54%) of the health care workers tested had no T-cell response to Omicron S1 regardless of their previous history of infection.

They designed a peptide pool containing all S1 and S2 mutations in Omicron and a matching pool of equivalent sequences of Wuhan Hu-1. The T cell response to the omicron peptide pool was reduced compared to the Hu-1 pool. Approximately 42% of healthcare professionals did not show a T cell response to the Omicron mutant pool.

Boosted healthcare professionals were studied for B-cell responses that experienced breakthrough infections during the Omicron wave 14 weeks after the third vaccination. Healthcare workers boosted by previous Wuhan Hu-1 infections infected during the Omicron wave had the highest N antibody binding. Infect-free boosted healthcare professionals produced a significantly elevated cross-reactive antibody binding response to all VOCs, including Omicron. Nevertheless, RBD binding and nAb IC₅₀ Depleted against Omicron compared to Wuhan Hu-1.

In particular, SARS-CoV-2 inexperienced health care workers who were not infected with Omicron infection did not induce nAbIC.₅₀ A response indicating a rapid loss of protection after boosters. Fourteen weeks after the third dose, 90% of uninfected healthcare workers showed no cross-reactive T cell response to Omicron S1. The T cell response after Omicron infection in previously naive health care workers was significantly reduced relative to Omicron S1 compared to Wuhan Hu-1 or Delta VOC S1.

In addition, health care workers with a history of infection during the Wuhan Hu-1 wave did not respond to Omicron S1. This indicates that Omicron infection was unable to enhance T cell immunity to itself. This meant that people infected with Wuhan Hu-1 early in the pandemic and re-infected with Omicron did not show increased T-cell immunity.

Finally, the team found that 16-18 weeks after infection with Wuhan Hu-1 or Alpha VOC, unvaccinated health workers lacked detectable cross-reactive RBD antibodies to the Omicron variant. Shown. The combination of previous infection and single vaccination significantly increased S1RBD-binding antibody against Omicron compared to the response of naive health care workers. However, the decline of Omicron RBD antibody was apparent among healthcare workers infected during the alpha wave 20-21 weeks after the second vaccination.

Fourteen weeks after booster administration, an increase in Omicron RBD binding response was observed among previously naive healthcare workers during the Omicron wave. In contrast, those previously infected with Wuhan Hu-1 did not show this increase. This meant that previous infection with the imprinted Hu-1 strain did not promote an antibody-binding response to Omicron, despite infection with the mutant itself.

Conclusion

In summary, the authors showed that B and T cell immunity to previous VOCs was increased in boosted healthcare professionals but decreased to SARS-CoV-2 omicrons. They say that the high global prevalence of SARS-CoV-2 omicron infection and reinfection may reflect a substantial disruption of recognition at B cell, T cell, nAb, and antibody binding levels. Showed to be high. In addition, certain imprinting combinations, such as infections between Wuhan Hu-1 waves and Omicron waves, can cause responsiveness disorders.