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The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses.

ABSTRACT: Pre-existing cross-reactive immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in infection-naive subjects have been described by several studies. In particular, regions of high homology between SARS-CoV-2 and common cold coronaviruses have been highlighted as a likely source of this cross-reactivity. However, the role of such cross-reactive responses in the outcome of SARS-CoV-2 infection and vaccination is currently unclear. Here, we review evidence regarding the impact of pre-existing humoral and T cell immune responses to outcomes of SARS-CoV-2 infection and vaccination. Furthermore, we discuss the importance of conserved coronavirus epitopes for the rational design of pan-coronavirus vaccines and consider cross-reactivity of immune responses to ancestral SARS-CoV-2 and SARS-CoV-2 variants, as well as their impact on COVID-19 vaccination.

SUBMITTER: Murray SM

PROVIDER: S-EPMC9765363 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses.

Murray Sam M SM Ansari Azim M AM Frater John J Klenerman Paul P Dunachie Susanna S Barnes Eleanor E Ogbe Ane A

Nature reviews. Immunology 20221220 5

Pre-existing cross-reactive immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in infection-naive subjects have been described by several studies. In particular, regions of high homology between SARS-CoV-2 and common cold coronaviruses have been highlighted as a likely source of this cross-reactivity. However, the role of such cross-reactive responses in the outcome of SARS-CoV-2 infection and vaccination is currently unclear. Here, we review evidence regar ...[more]

PMID: 36539527

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Project description:The contributions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells to vaccine efficacy and durability are unclear. We investigated relationships between mRNA vaccine-induced spike-specific interferon- gamma (IFN-γ) and interleukin-2 (IL-2) T-cell responses and neutralizing antibody development in long-term care home staff doubly vaccinated with BNT162b2 or mRNA-1273. The impacts of pre-existing cross-reactive T-cell immunity on cellular and humoral responses to vaccination were additionally assessed. Mathematical modeling of the kinetics of spike-specific IFN-γ and IL-2 T-cell responses over 6 months post-second dose was bifurcated into recipients who exhibited gradual increases with doubling times of 155 and 167 days or decreases with half-lives of 165 and 132 days, respectively. Differences in kinetics did not correlate with clinical phenotypes. Serological anti-spike IgG, anti-receptor binding domain (RBD) IgG, anti-spike IgA, and anti-RBD IgA antibody levels otherwise decayed in all participants with half-lives of 63, 57, 79, and 46 days, respectively, alongside waning neutralizing capacity (t1/2 = 408 days). Spike-specific T-cell responses induced at 2-6 weeks positively correlated with live viral neutralization at 6 months post-second dose, especially in hybrid immune individuals. Participants with pre-existing cross-reactive T-cell immunity to SARS-CoV-2 exhibited greater spike-specific T-cell responses, reduced anti-RBD IgA antibody levels, and a trending increase in neutralization at 2-6 weeks post-second dose. Non-spike-specific T-cells predominantly targeted SARS-CoV-2 non-structural protein at 6 months post-second dose in cross-reactive participants. mRNA vaccination was lastly shown to induce off-target T-cell responses against unrelated antigens. In summary, vaccine-induced spike-specific T-cell immunity appeared to influence serological neutralizing capacity, with only a modest effect induced by pre-existing cross-reactivity.ImportanceOur findings provide valuable insights into the potential contributions of mRNA vaccine-induced spike-specific T-cell responses to the durability of neutralizing antibody levels in both uninfected and hybrid immune recipients. Our study additionally sheds light on the precise impacts of pre-existing cross-reactive T-cell immunity to severe acute respiratory syndrome coronavirus 2 on the magnitude and kinetics of cellular and humoral responses to vaccination. Accordingly, our data will help optimize the development of next-generation T cell-based coronavirus vaccines and vaccine regimens to maximize efficacy and durability.

Project description:In December 2019, a new coronavirus, SARS-CoV-2, was found to in Wuhan, China. Cases of infection were subsequently detected in other countries in a short period of time, resulting in the declaration of the COVID-19 pandemic by the World Health Organization (WHO) on 11 March 2020. Questions about the impact of herd immunity of pre-existing immune reactivity to SARS-CoV-2 on COVID-19 severity, associated with the immunity to seasonal manifestation, are still to be resolved and may be useful for understanding some processes that precede the emergence of a pandemic virus. Perhaps this will contribute to understanding some of the processes that precede the emergence of a pandemic virus. We assessed the specificity and virus-neutralizing capacity of antibodies reacting with the nucleocapsid and spike proteins of SARS-CoV-2 in a set of serum samples collected in October and November 2019, before the first COVID-19 cases were documented in this region. Blood serum samples from 799 residents of several regions of Siberia, Russia, (the Altai Territory, Irkutsk, Kemerovo and Novosibirsk regions, the Republic of Altai, Buryatia, and Khakassia) were analyzed. Sera of non-infected donors were collected within a study of seasonal influenza in the Russian Federation. The sample collection sites were located near the flyways and breeding grounds of wild waterfowl. The performance of enzyme-linked immunosorbent assay (ELISA) for the collected sera included the usage of recombinant SARS-CoV-2 protein antigens: full-length nucleocapsid protein (CoVN), receptor binding domain (RBD) of S-protein and infection fragment of the S protein (S5-6). There were 183 (22.9%) sera reactive to the S5-6, 270 (33.8%) sera corresponding to the full-length N protein and 128 (16.2%) sera simultaneously reactive to both these proteins. Only 5 out of 799 sera had IgG antibodies reactive to the RBD. None of the sera exhibited neutralizing activity against the nCoV/Victoria/1/2020 SARS-CoV-2 strain in Vero E6 cell culture. The data obtained in this study suggest that some of the population of the analyzed regions of Russia had cross-reactive humoral immunity against SARS-CoV-2 before the COVID-19 pandemic started. Moreover, among individuals from relatively isolated regions, there were significantly fewer reliably cross-reactive sera. The possible significance of these data and impact of cross-immunity to SARS-CoV-2 on the prevalence and mortality of COVID-19 needs further assessment.

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The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses.

Publications

The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses.

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