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SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans.

ABSTRACT: SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4⁺ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4⁺ T (T_FH) cell responses contribute to this outstanding immunogenicity. Using fine-needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we evaluated the T cell receptor sequences and phenotype of lymph node T_FH. Mining of the responding T_FH T cell receptor repertoire revealed a strikingly immunodominant HLA-DPB1^∗04-restricted response to S_167-180 in individuals with this allele, which is among the most common HLA alleles in humans. Paired blood and lymph node specimens show that while circulating S-specific T_FH cells peak one week after the second immunization, S-specific T_FH persist at nearly constant frequencies for at least six months. Collectively, our results underscore the key role that robust T_FH cell responses play in establishing long-term immunity by this efficacious human vaccine.

SUBMITTER: Mudd PA

PROVIDER: S-EPMC8695127 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Study questionDoes the immune response to coronavirus disease 2019 (COVID-19) infection or the BNT162b2 mRNA vaccine involve the ovarian follicle, and does it affect its function?Summary answerWe were able to demonstrate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG in follicular fluid (FF) from both infected and vaccinated IVF patients, with no evidence for compromised follicular function.What is known alreadyNo research data are available yet.Study design, size, durationThis is a cohort study, composed of 32 consecutive IVF patients, either infected with COVID-19, vaccinated or non-exposed, conducted between 1 February and 10 March 2021 in a single university hospital-based IVF clinic.Participants/materials, setting, methodsA consecutive sample of female consenting patients undergoing oocyte retrieval was recruited and assigned to one of the three study groups: recovering from confirmed COVID-19 (n = 9); vaccinated (n = 9); and uninfected, non-vaccinated controls (n = 14). Serum and FF samples were taken and analyzed for anti-COVID IgG as well as estrogen, progesterone and heparan sulfate proteoglycan 2 concentration, as well as the number and maturity of aspirated oocytes and day of trigger estrogen and progesterone measurements. Main outcome measures were follicular function, including steroidogenesis, follicular response to the LH/hCG trigger, and oocyte quality biomarkers.Main results and the role of chanceBoth COVID-19 and the vaccine elicited anti-COVID IgG antibodies that were detected in the FF at levels proportional to the IgG serum concentration. No differences between the three groups were detected in any of the surrogate parameters for ovarian follicle quality.Limitations, reasons for cautionThis is a small study, comprising a mixed fertile and infertile population, and its conclusions should be supported and validated by larger studies.Wider implications of the findingsThis is the first study to examine the impact of SARS-Cov-2 infection and COVID-19 vaccination on ovarian function and these early findings suggest no measurable detrimental effect on function of the ovarian follicle.Study funding/competing interest(s)The study was funded out of an internal budget. There are no conflicts of interest for any of the authors.Trial registration numberCinicalTrials.gov registry number NCT04822012.

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SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans.

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