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Prior vaccination enhances immune responses during SARS-CoV-2 breakthrough infection with early activation of memory T cells followed by production of potent neutralizing antibodies.

ABSTRACT: SARS-CoV-2 infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave. These studies revealed heightened Spike-specific responses during infection of vaccinated compared to unvaccinated individuals. Spike-specific CD4 T cells and plasmablasts expanded and CD8 T cells were robustly activated during the first week. In contrast, memory B cell activation, neutralizing antibody production, and primary responses to non-Spike antigens occurred during the second week. Collectively, these data demonstrate the functionality of vaccine-primed immune memory and highlight memory T cells as rapid responders during SARS-CoV-2 infection.

SUBMITTER: Painter MM

PROVIDER: S-EPMC9934532 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Prior vaccination enhances immune responses during SARS-CoV-2 breakthrough infection with early activation of memory T cells followed by production of potent neutralizing antibodies.

Painter Mark M MM Johnston Timothy S TS Lundgreen Kendall A KA Santos Jefferson J S JJS Qin Juliana S JS Goel Rishi R RR Apostolidis Sokratis A SA Mathew Divij D Fulmer Bria B Williams Justine C JC McKeague Michelle L ML Pattekar Ajinkya A Goode Ahmad A Nasta Sean S Baxter Amy E AE Giles Josephine R JR Skelly Ashwin N AN Felley Laura E LE McLaughlin Maura M Weaver Joellen J Kuthuru Oliva O Dougherty Jeanette J Adamski Sharon S Long Sherea S Kee Macy M Clendenin Cynthia C da Silva Antunes Ricardo R Grifoni Alba A Weiskopf Daniela D Sette Alessandro A Huang Alexander C AC Rader Daniel J DJ Hensley Scott E SE Bates Paul P Greenplate Allison R AR Wherry E John EJ

bioRxiv : the preprint server for biology 20230206

SARS-CoV-2 infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immu ...[more]

PMID: 36798171

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Project description:Despite the success of COVID-19 vaccines in preventing infection and/or severe disease, there has been an increase in SARS-CoV-2 infections in vaccinated individuals owing to the waning vaccine-derived immunity, and the emergence of new variants which encode escape mutations in Spike. Following breakthrough infection in vaccinated individuals, an increase in neutralization breadth has been observed in sera/plasma. However, how exposure to a heterologous Spike broadens the neutralizing response at the monoclonal antibody (mAb) level is not fully understood. Through isolation of 119 mAbs from three individuals receiving two doses of BNT162b2 vaccine before becoming Delta or Omicron/BA.1 infected, we show that serum breadth occurs due to the presence of somatically mutated mAbs with broad neutralization activity indicative of re-activation and maturation of B cells generated through previous COVID-19 vaccination. Isolated mAbs frequently show reduced neutralization of current circulating variants including BA.2.75.2, XBB, XBB.1.5, and BQ.1.1 confirming continuous selective pressure on Spike to evolve and evade neutralization. However, isolation of mAbs that display effective cross-neutralization against all variants indicates the presence of conserved epitopes on the receptor binding domain and a lesser extent the N-terminal domain. These findings have implications for the selection of Spike antigens for next-generation COVID-19 vaccines. IMPORTANCE With the emergence of SARS-CoV-2 viral variants, there has been an increase in infections in vaccinated individuals. Here, we isolated monoclonal antibodies (mAbs) from individuals experiencing a breakthrough infection (Delta or BA.1) to determine how exposure to a heterologous Spike broadens the neutralizing antibody response at the monoclonal level. All mAbs isolated had reactivity to the Spike of the vaccine and infection variant. While many mAbs showed reduced neutralization of current circulating variants, we identified mAbs with broad and potent neutralization of BA.2.75.2, XBB, XBB.1.5, and BQ.1.1 indicating the presence of conserved epitopes on Spike. These results indicate that variant-based vaccine boosters have the potential to broaden the vaccine response.

Dataset Information

Prior vaccination enhances immune responses during SARS-CoV-2 breakthrough infection with early activation of memory T cells followed by production of potent neutralizing antibodies.

Publications

Prior vaccination enhances immune responses during SARS-CoV-2 breakthrough infection with early activation of memory T cells followed by production of potent neutralizing antibodies.

Similar Datasets

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