Omicron infection increases IgG binding to spike protein of predecessor variants

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in India in 2020-2022 was driven predominantly by Wild (Wuhan-Hu-1 and D614G), Delta, and Omicron variants. The aim of this study was to examine the effect of infections on the humoral immune response and cross-reactivity to spike proteins of Wuhan-Hu-1, Delta, C.1.2., and Omicron. Residual archival sera (N = 81) received between January 2020 and March 2022 were included. Infection status was inferred by a positive SARS-CoV-2 RT-PCR and/or serology (anti-N and anti-S antibodies) and sequencing of contemporaneous samples (N = 18) to infer lineage. We estimated the levels and cross-reactivity of infection-induced sera including Wild, Delta, Omicron as well as vaccine breakthrough infections (Delta and Omicron). We found an approximately two-fold increase in spike-specific IgG antibody binding in post-Omicron infection compared with the pre-Omicron period, whilst the change in preand post-Delta infections were similar. Further investigation of Omicron-specific humoral responses revealed primary Omicron infection as an inducer of crossreactive antibodies against predecessor variants, in spite of the weaker degree of humoral response compared to Wuhan-Hu-1 and Delta infection. Intriguingly, Omicron vaccine-breakthrough infections when compared with primary infections, exhibited increased humoral responses against RBD (7.7-fold) and Trimeric S (Trimeric form of spike protein) (34.6-fold) in addition to increased binding of IgGs towards previously circulating variants (4.2 -6.5-fold). Despite Delta breakthrough infections showing a higher level of humoral response against RBD (2.9-fold) and Trimeric S (5.7-fold) compared to primary Delta sera, a demonstrably reduced binding (36%-49%) was observed to Omicron spike protein. Omicron vaccine breakthrough infection results in increased intensity of humoral response and wider breadth of IgG binding to spike proteins of antigenically-distinct, predecessor variants.

Omicron infection-associated T- and B-cell immunity in antigen-naive and triple-COVID-19-vaccinated individuals

“…Recent studies (11)(12)(13)(14) have observed a limited variant-specific cross-neutralizing immunity after Omicron breakthrough infection. In line with our data, we suggest that Omicron breakthrough infections are less immunogenic than, for example, Delta, thus providing reduced protection against reinfection or infection from future variants.…”

Humoral Immune Responses in Patients with Severe COVID-19: A Comparative Pilot Study between Individuals Infected by SARS-CoV-2 during the Wild-Type and the Delta Periods

“…An alternative approach to evaluate variant-specific immunization is to compare serum samples from patients who had a prior infection with different SARS-CoV-2 variants in terms of their cross-reactivity. However, only a few detailed reports on this subject have been published [ 8 , 9 ]. In particular, it was demonstrated that Omicron infections lead to increased antibody binding to pre-Omicron S variants [ 9 ]; at the same time, sera from the Delta and pre-Delta periods were similar in binding to S protein variants.…”

“…However, only a few detailed reports on this subject have been published [ 8 , 9 ]. In particular, it was demonstrated that Omicron infections lead to increased antibody binding to pre-Omicron S variants [ 9 ]; at the same time, sera from the Delta and pre-Delta periods were similar in binding to S protein variants. In order to compare more comprehensively the humoral immunity in patients from the D614G and Delta periods, we used a set of methods, both standard (ELISA, pVNA, and sVNA) and especially designed for this case (fcVNA and mELISA).…”

“…Despite a large amount of accumulated data, limited attention has been paid to direct comparison of immunity after COVID-19 caused by the different variants of SARS-CoV-2 [ 8 , 9 , 10 ]. In order to fill this knowledge gap, we examined the levels of humoral responses induced by natural infection with SARS-CoV-2 variants causing the COVID-19 in Moscow, Russia.…”

Overview of immunological & virological factors driving the evolution & global spread of SARS-CoV-2 variants

“…Memory B cells formed in response to primary and secondary vaccination with S from an ancestral SARS-CoV-2 strain tend to be preferentially restimulated by a third boosting immunization with Omicron BA.1 S in a process termed antigen imprinting 83 - 85 . This is due to memory B cells preferentially recognizing S epitopes in BA.1 shared with the vaccine strain and results in antibodies that are relatively ineffective in neutralizing BA.1 84 , 85 . However, small numbers of B cells recognizing novel epitopes present in BA.1 that were not present in ancestral S were also stimulated on immunizing with BA.1 S 83 .…”