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Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history.

ABSTRACT: Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in many individuals possessing hybrid immunity, generated through a combination of vaccination and infection. Concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that prior SARS-CoV-2 infection is associated with immune dampening. Taking a broad and comprehensive approach, we characterize mucosal and blood immunity to spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without prior SARS-CoV-2 infection. We find that most individuals increase BA.1/BA.2/BA.5-specific neutralizing antibodies following infection, but confirm that the magnitude of increase and post-omicron titres are higher in the infection-naive. In contrast, significant increases in nasal responses, including neutralizing activity against BA.5 spike, are seen regardless of infection history. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are significantly higher in the previously-infected, who display a maximally induced response with a highly cytotoxic CD8+ phenotype following their 3^rd mRNA vaccine dose. Responses to non-spike antigens increase significantly regardless of prior infection status. These findings suggest that hybrid immunity induced by omicron breakthrough infections is characterized by significant immune enhancement that can help protect against future omicron variants.

SUBMITTER: Hornsby H

PROVIDER: S-EPMC10442364 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history.

Hornsby Hailey H Nicols Alexander R AR Longet Stephanie S Liu Chang C Tomic Adriana A Angyal Adrienn A Kronsteiner Barbara B Tyerman Jessica K JK Tipton Tom T Zhang Peijun P Gallis Marta M Supasa Piyada P Selvaraj Muneeswaran M Abraham Priyanka P Neale Isabel I Ali Mohammad M Barratt Natalie A NA Nell Jeremy M JM Gustafsson Lotta L Strickland Scarlett S Grouneva Irina I Rostron Timothy T Moore Shona C SC Hering Luisa M LM Dobson Susan L SL Bibi Sagida S Mongkolsapaya Juthathip J Lambe Teresa T Wootton Dan D Hall Victoria V Hopkins Susan S Dong Tao T Barnes Eleanor E Screaton Gavin G Richter Alex A Turtle Lance L Rowland-Jones Sarah L SL Carroll Miles M Duncan Christopher J A CJA Klenerman Paul P Dunachie Susanna J SJ Payne Rebecca P RP de Silva Thushan I TI

Nature communications 20230821 1

Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in many individuals possessing hybrid immunity, generated through a combination of vaccination and infection. Concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that prior SARS-CoV-2 infection is associated with immune dampening. Taking a broad and comprehensive approach, we characterize mucosal and blood immunity to spike ...[more]

PMID: 37604803

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Project description:BackgroundThe spread of the vaccine-resistant Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens unvaccinated and fully vaccinated individuals, and accelerated booster vaccination campaigns are underway to mitigate the ongoing wave of Omicron cases. The immunity provided by standard vaccine regimens, boosted regimens, and immune responses elicited by vaccination plus natural infection remain incompletely understood. The magnitude, quality, and durability of serological responses, and the likelihood of protection against future SARS-CoV-2 variants following these modes of exposure, are poorly characterized but are critical to the future trajectory of the coronavirus disease 2019 (COVID-19) pandemic.MethodsNinety-nine individuals were semi-randomly selected from a larger vaccination cohort following vaccination and, in some cases, breakthrough infection. We analyzed spike receptor-binding domain-specific immunoglobulin G (IgG), IgA, and IgM by enzyme-linked immunosorbent assay, neutralizing antibody titers against live SARS-CoV-2 variants, and antibody-dependent cell-mediated phagocytosis.FindingsIn 99 vaccinated adults, compared with responses after two doses of an mRNA regimen, the immune responses 3 months after a third vaccine dose and 1 month after breakthrough infection due to prior variants show dramatic increases in magnitude, potency, and breadth, including increased antibody-dependent cellular phagocytosis and robust neutralization of the currently circulating Omicron BA.2 variant.ConclusionsBoosters and natural infection substantially boost immune responses. As the number of Omicron sub-variant cases rise and as global vaccination and booster campaigns continue, an increasing proportion of the world's population will acquire potent immune responses that may be protective against future SARS-CoV-2 variants.FundingThis work was funded by the M. J. Murdock Charitable Trust, the OHSU Foundation, the NIH (T32HL083808), and OHSU Innovative IDEA.

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Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history.

Publications

Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history.

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