How does previous SARS-CoV-2 infection affect the B-cell receptor repertoire in response to vaccination?

In a recent study published in vaccinationresearchers evaluated the immune response by B lymphocytes to Pfizer’s severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA (messenger ribonucleic acid) vaccine.

Background

Characterizing B-lymphocyte responses to coronavirus disease 2019 (COVID-19) vaccines from previous SARS-CoV-2 exposures will enhance our understanding of the potential use of B-cell memory by vaccines. Higher somatic hypermutation (SHM) rates have been reported in response to natural SARS-CoV-2 infection, but not vaccination, indicating a distinct B-cell receptor (BCR) response to natural infection . Common (or published) SARS-CoV-2 clonotypes have been reported among a wide variety of individuals, indicating evolutionary convergence across the repertoire.

The authors of this study previously reported that anti-SARS-CoV-2 S titers in response to SARS-CoV-2 vaccination were higher in seropositive (COVID-19 -19) reported higher). However, the impact of previous SARS-CoV-2 exposure on the immune response of her BCR repertoire to COVID-19 vaccination is unknown.

About research

In this study, investigators comparatively assess the BCR repertoire of seropositive and seronegative individuals to assess the impact of previous COVID-19 medical history on B-lymphocyte responses to the Pfizer SARS-CoV-2 mRNA vaccine. We extended our previous analysis by They also investigated potential BCR public clonotype induction by vaccines.

Four seronegative and five seropositive health care workers (HCW) were enrolled in the study. Previous SARS-CoV-2 exposure, confirmed by polymerase chain reaction (PCR), occurred 1–2 months before his study initiation. Pre-vaccination and 21 days after vaccination he had a blood sample taken, then serum and her PBMCs (peripheral blood mononuclear cells) were used for antibodies (Abs). titer Determination and BCR sequencing, respectively. Immunoanalyses were performed to assess variable (V) gene usage, heavy chain complementarity determining region 3 (HCDR3) length, SHM rate, clonality, and convergence.

Fluorescence flow cytometry (FC) was used to determine antibody titers against SARS-CoV-2 spike (S) protein subunits 1 (S1) and 2 (S2), nucleocapsid (N) protein, and receptor binding domain. A base analysis was performed. (RBD), using secondary antibodies of the isotypes immunoglobulin G (IgG), IgA, and IgM. BCR sequences containing IgG isotypes were analyzed for variable gene family (IGHV) usage and V gene usage was assessed for he IgM or IgA.

Differences in IgG repertoires in response to vaccination were assessed using species richness, Simpson’s diversity index, and Shannon’s diversity index. The existing IgG repertoire clones and the 50 most abundant IgG clones were further analyzed. Expansion of IgG (from previous infection) clones in response to vaccination was assessed and V gene usage, SHM, and HCDR3 length of 28 convergent clones shared by all study participants were characterized. rice field. The COVID Ab database was consulted to determine whether the converging and expanding clones identified in this study had previously been identified as SARS-CoV-2-specific clones.

result

Vaccine-induced expanded IgG clonotypes had shorter HCDR3 lengths, and expanded clonotypes had higher rates of SHM in seropositive individuals. Public chronotypes (n=28) were identified in all individuals with higher SHM and shorter HCDR3 than other chronotypes. This indicates convergent evolution with vaccination, regardless of previous SARS-CoV-2 exposure. Serum titers of IgG, IgM, and IgA isotypes against SARS-CoV-2 S1, S2, RBD, and NP were detected, the lowest and highest titers of IgA and IgG were detected, respectively, and Ab titers were based on The number of seropositive subjects at the line was higher.

Three weeks after vaccination, seropositive IgG titers against S1, S2, and NP continued to be greater than seronegative titers. However, the anti-SRBD IgG titers were identical. Anti-S2 IgM titers were greater among seropositive individuals, whereas IgG titers against RBD, NP and S1, RBD did not differ between serotypes.However, IgA titers were not significantly different between SARS-CoV-2 serotypes antigen.

HCDR3 length distribution, global BCR isotype, and IGHV usage were not altered by vaccination. The IgM isotype had the highest frequency across serotypes (67% seropositive, 62% seronegative). IgG BCR sequences used IGHV3 with the highest frequency. V-gene usage and HCDR3 length of IgM and IgA of BCR sequences were not statistically different between serotypes 21 days after vaccination.

BCR SHM rates increased after vaccination in seropositive individuals and decreased in seronegative individuals. Comparing his IgG SHM rates at the two time points, he found no difference in the proportion of clones with less than 2 mutations or more than 2 mutations between groups. However, the SHM rate was higher for his IgG sequences with two or more mutations among seronegative individuals at both time points. His BCR SHM of IgA rate was significantly increased after his 3-week vaccination of seropositive, but showed no significant difference among post-vaccination seronegative persons.

The SHM patterns of IgM and IgG were similar. At the second time point, seropositive BCR clones showed more Shannon diversity and species richness than seronegative ones. Both serotypes had pre-existing clonotypes that expanded after vaccination. However, the repertoire was dominated by novel clones. Minimal overlap was observed between the 50 most numerous his IgG clonotypes at 21 days post-vaccination and clones of any isotype at baseline.

V gene usage by the 50 most abundant clones did not differ significantly from the others across serotypes. was shorter than the clone of SHM rates were higher in the top 50 seropositive clones and other clones than in those seronegative clones. The queried chronotypes showed 3 matches with the COVID-19 Ab database. Clones #34727 and #13327 matched S-B8 and Fab-368 Abs, respectively, both of which were able to neutralize SARS-CoV-2. Clone #8269 matched several Ab targets but had no SARS-CoV-2 neutralization.

Conclusion

In conclusion, based on research results, people with a history of COVID-19 had higher antibody titers after the first SARS-CoV-2 vaccination.