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J Med Virol . Omicron infection increases IgG binding to spike protein of predecessor variants

tetano

Editor, Senior Moderator
J Med Virol


. 2022 Dec 22.
doi: 10.1002/jmv.28419. Online ahead of print.
Omicron infection increases IgG binding to spike protein of predecessor variants


Gokulnath Mahalingam[SUP] 1 [/SUP], Yogapriya Periyasami[SUP] 1 [/SUP], Porkizhi Arjunan[SUP] 1 [/SUP], Rajesh Kumar Subaschandrabose[SUP] 2 [/SUP], Tamil Venthan Mathivanan[SUP] 2 [/SUP], Roshlin Susan Mathew[SUP] 2 [/SUP], Kt Ramya Devi[SUP] 3 [/SUP], Prasanna Samuel Premkumar[SUP] 4 [/SUP], Jayaprakash Muliyil[SUP] 5 [/SUP], Alok Srivastava[SUP] 1 [/SUP], Mahesh Moorthy[SUP] 2 [/SUP], Srujan Marepally[SUP] 1 [/SUP]



Affiliations

Abstract

Background: SARS-CoV-2 transmission in India in 2020-2022 was driven predominantly by Wild (Wuhan-Hu-1and 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.
Objectives: 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).
Results: We found ~2-fold increase in spike-specific IgG antibody binding in post-Omicron infection compared to the pre-Omicron period, whilst the change in pre- and post-Delta infections were similar. Further investigation of Omicron-specific humoral responses revealed primary Omicron infection as an inducer of cross-reactive antibodies against predecessor variants, in spite of 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.
Conclusions: 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. This article is protected by copyright. All rights reserved.

Keywords: Breakthrough infection; Delta; Humoral immunity; Immune responses; Omicron; SARS coronavirus; SARS-CoV-2 spike variants.
 
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