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Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine.

ABSTRACT: Despite a clear role in protective immunity, the durability and quality of antibody and memory B cell responses induced by mRNA vaccination, particularly by a 3 ^rd dose of vaccine, remains unclear. Here, we examined antibody and memory B cell responses in a cohort of individuals sampled longitudinally for ∼9-10 months after the primary 2-dose mRNA vaccine series, as well as for ∼3 months after a 3 ^rd mRNA vaccine dose. Notably, antibody decay slowed significantly between 6- and 9-months post-primary vaccination, essentially stabilizing at the time of the 3 ^rd dose. Antibody quality also continued to improve for at least 9 months after primary 2-dose vaccination. Spike- and RBD-specific memory B cells were stable through 9 months post-vaccination with no evidence of decline over time, and ∼40-50% of RBD-specific memory B cells were capable of simultaneously recognizing the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells induced by the first 2 doses of mRNA vaccine were boosted significantly by a 3rd dose and the magnitude of this boosting was similar to memory B cells specific for other variants. Pre-3 ^rd dose memory B cell frequencies correlated with the increase in neutralizing antibody titers after the 3 ^rd dose. In contrast, pre-3 ^rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit reactivation of immunological memory and constrain further antibody boosting by mRNA vaccines. These data provide a deeper understanding of how the quantity and quality of antibody and memory B cell responses change over time and number of antigen exposures. These data also provide insight into potential immune dynamics following recall responses to additional vaccine doses or post-vaccination infections.

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SUBMITTER: Goel RR

PROVIDER: S-EPMC8887077 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine.

Goel Rishi R RR Painter Mark M MM Lundgreen Kendall A KA Apostolidis Sokratis A SA Baxter Amy E AE Giles Josephine R JR Mathew Divij D Pattekar Ajinkya A Reynaldi Arnold A Khoury David S DS Gouma Sigrid S Hicks Philip P Dysinger Sarah S Hicks Amanda A Sharma Harsh H Herring Sarah S Korte Scott S Kc Wumesh W Oldridge Derek A DA Erickson Rachel I RI Weirick Madison E ME McAllister Christopher M CM Awofolaju Moses M Tanenbaum Nicole N Dougherty Jeanette J Long Sherea S D'Andrea Kurt K Hamilton Jacob T JT McLaughlin Maura M Williams Justine C JC Adamski Sharon S Kuthuru Oliva O Drapeau Elizabeth M EM Davenport Miles P MP Hensley Scott E SE Bates Paul P Greenplate Allison R AR Wherry E John EJ

bioRxiv : the preprint server for biology 20220222

Despite a clear role in protective immunity, the durability and quality of antibody and memory B cell responses induced by mRNA vaccination, particularly by a 3 <sup>rd</sup> dose of vaccine, remains unclear. Here, we examined antibody and memory B cell responses in a cohort of individuals sampled longitudinally for ∼9-10 months after the primary 2-dose mRNA vaccine series, as well as for ∼3 months after a 3 <sup>rd</sup> mRNA vaccine dose. Notably, antibody decay slowed significantly between 6- ...[more]

PMID: 35233575

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Project description:IntroductionThe prime-boost COVID-19 mRNA vaccination strategy has proven to be effective against severe COVID-19 disease and death. However, concerns have been raised due to decreasing neutralizing antibody levels after COVID-19 vaccination and due to the emergence of new immuno-evasive SARS-CoV-2 variants that may require additional booster vaccinations.MethodsIn this study, we analyzed the humoral and cell-mediated immune responses against the Omicron BA.1 and BA.2 subvariants in Finnish healthcare workers (HCWs) vaccinated with three doses of COVID-19 mRNA vaccines. We used enzyme immunoassay and microneutralization test to analyze the levels of SARS-CoV-2 specific IgG antibodies in the sera of the vaccinees and the in vitro neutralization capacity of the sera. Activation induced marker assay together with flow cytometry and extracellular cytokine analysis was used to determine responses in SARS-CoV-2 spike protein stimulated PBMCs.ResultsHere we show that within the HCWs, the third mRNA vaccine dose recalls both humoral and T cell-mediated immune responses and induces high levels of neutralizing antibodies against Omicron BA.1 and BA.2 variants. Three weeks after the third vaccine dose, SARS-CoV-2 wild type spike protein-specific CD4+ and CD8+ T cells are observed in 82% and 71% of HCWs, respectively, and the T cells cross-recognize both Omicron BA.1 and BA.2 spike peptides. Although the levels of neutralizing antibodies against Omicron BA.1 and BA.2 decline 2.5 to 3.8-fold three months after the third dose, memory CD4+ T cell responses are maintained for at least eight months post the second dose and three months post the third vaccine dose.DiscussionWe show that after the administration of the third mRNA vaccine dose the levels of both humoral and cell-mediated immune responses are effectively activated, and the levels of the spike-specific antibodies are further elevated compared to the levels after the second vaccine dose. Even though at three months after the third vaccine dose antibody levels in sera decrease at a similar rate as after the second vaccine dose, the levels of spike-specific CD4+ and CD8+ T cells remain relatively stable. Additionally, the T cells retain efficiency in cross-recognizing spike protein peptide pools derived from Omicron BA.1 and BA.2 subvariants. Altogether our results suggest durable cellmediated immunity and protection against SARS-CoV-2.

Project description:ObjectivesThe rapid spread of the SARS-CoV-2 Omicron variant has raised concerns regarding waning vaccine-induced immunity and durability. We evaluated protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant and its sublineages.DesignSystematic review and meta-analysis.Data sourcesElectronic databases and other resources (PubMed, Embase, CENTRAL, MEDLINE, CINAHL PLUS, APA PsycINFO, Web of Science, Scopus, ScienceDirect, MedRxiv and bioRxiv) were searched until December 2022.Study eligibility criteriaWe included studies that assessed the effectiveness of mRNA vaccine booster doses against SARS-CoV-2 infection and severe COVID-19 outcomes caused by the subvariant.Data extraction and synthesisEstimates of vaccine effectiveness (VE) at different time points after the third-dose and fourth-dose vaccination were extracted. Random-effects meta-analysis was used to compare VE of the third dose versus the primary series, no vaccination and the fourth dose at different time points. The certainty of the evidence was assessed by Grading of Recommendations, Assessments, Development and Evaluation approach.ResultsThis review included 50 studies. The third-dose VE, compared with the primary series, against SARS-CoV-2 infection was 48.86% (95% CI 44.90% to 52.82%, low certainty) at ≥14 days, and gradually decreased to 38.01% (95% CI 13.90% to 62.13%, very low certainty) at ≥90 days after the third-dose vaccination. The fourth-dose VE peaked at 14-30 days (56.70% (95% CI 50.36% to 63.04%), moderate certainty), then quickly declined at 61-90 days (22% (95% CI 6.40% to 37.60%), low certainty). Compared with no vaccination, the third-dose VE was 75.84% (95% CI 40.56% to 111.12%, low certainty) against BA.1 infection, and 70.41% (95% CI 49.94% to 90.88%, low certainty) against BA.2 infection at ≥7 days after the third-dose vaccination. The third-dose VE against hospitalisation remained stable over time and maintained 79.30% (95% CI 58.65% to 99.94%, moderate certainty) at 91-120 days. The fourth-dose VE up to 60 days was 67.54% (95% CI 59.76% to 75.33%, moderate certainty) for hospitalisation and 77.88% (95% CI 72.55% to 83.21%, moderate certainty) for death.ConclusionThe boosters provided substantial protection against severe COVID-19 outcomes for at least 6 months, although the duration of protection remains uncertain, suggesting the need for a booster dose within 6 months of the third-dose or fourth-dose vaccination. However, the certainty of evidence in our VE estimates varied from very low to moderate, indicating significant heterogeneity among studies that should be considered when interpreting the findings for public health policies.Prospero registration numberCRD42023376698.

Dataset Information

Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine.

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Publications

Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine.

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