SARS-CoV-2 Omicron Variant Prior Spike

In the current study, researchers investigated the degree to which infection with SARS-CoV-2 Omicron boosts cross-reactive B and T cell immunity against itself and other VOCs. The authors recruited a cohort of healthcare workers (HCWs) longitudinally followed from March 2020 to January 2022, who were individuals with different combinations of vaccination and infection histories.

HCWs were identified from successive COVID-19 waves, viz., Alpha, Delta, and Omicron, and after partial (first dose), full (double dose), and booster (third dose) vaccination with the BNT162b2 vaccine. The nucleocapsid (N) and spike 1 (S1) receptor-binding domain (RBD) serology were longitudinally evaluated. The authors observed that the third exposure to the spike boosted S1 RBD titers in most HCW after two or three weeks of the most recent vaccination.

Moreover, antibody responses were plateaued by the third vaccination. Triple-vaccinated HCWs infected with SARS-CoV-2 Wuhan Hu-1 had significantly reduced anti-RBD titers against Beta, Delta, and Omicron variants compared to SARS-CoV-2-naïve HCWs. Also, the cross-reactive anti-RBD immunoglobulin G (IgG) and nAb against Omicron VOC were significantly diminished compared to other variants regardless of infection history.

The frequency of memory B cells (MBCs) against the S protein of Wuhan Hu-1, Delta, and Omicron variants was boosted two to three weeks post-third vaccination compared to 20-21 weeks after the second dose. While the MBC frequency against S protein of Wuhan Hu-1 and Delta variant was similar irrespective of prior infection, it significantly declined against Omicron S1 two to three weeks after the booster dose and 20-21 weeks after the second dose.

RBD or whole S antibody and live virus nAb half-maximal inhibitory concentration (IC­­50) correlated for Alpha and Delta variants but not for Beta, Gamma, and Omicron, implying that antibody binding was a poor marker of nAb IC­50. Next, T cell responses were compared after two to three weeks of booster administration among HCWs who were SARS-CoV-2-naïve or had been infected with Wuhan Hu-1, Delta, or Omicron variants.

T cell immunity was compared against a mapped epitope pool (MEP) of Wuhan Hu-1 spike peptides with S1 from Wuhan Hu-1 or S1 proteins with Delta or Omicron mutations. The magnitude of response for S1 of Omicron was significantly low. Of note, more than half the tested HCWs (54%) had no T cell responses against Omicron S1 irrespective of prior infection history.

They designed a peptide pool encompassing all S1 and S2 mutations of Omicron and a matched pool of equivalent sequences of Wuhan Hu-1. T cell responses against the Omicron peptide pool were diminished compared to the Hu-1 pool. About 42% of HCWs did not have T cell responses against the Omicron variant mutant pool.

In Detail: https://www.tridhascholars.org/press-release/against-sars-cov-2-omicron-variant-prior-spike-protein-exposures-shape-protection.php

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