This article is a Preprint
Preprints are preliminary research reports that have not been certified by peer review. They should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.
Preprints posted online allow authors to receive rapid feedback and the entire scientific community can appraise the work for themselves and respond appropriately. Those comments are posted alongside the preprints for anyone to read them and serve as a post publication assessment.
Antibody feedback regulation of memory B cell development in SARS-CoV-2 mRNA vaccination
Preprint
in En
| PREPRINT-MEDRXIV
| ID: ppmedrxiv-22278483
ABSTRACT
Feedback inhibition of humoral immunity by antibodies was initially documented in guinea pigs by Theobald Smith in 1909, who showed that passive administration of excess anti-Diphtheria toxin inhibited immune responses1. Subsequent work documented that antibodies can enhance or inhibit immune responses depending on antibody isotype, affinity, the physical nature of the antigen, and engagement of immunoglobulin (Fc) and complement (C) receptors2, 3. However, little is known about how pre-existing antibodies might influence the subsequent development of memory B cells. Here we examined the memory B cell response in individuals who received two high-affinity IgG1 anti-SARS-CoV-2 receptor binding domain (RBD)-specific monoclonal antibodies, C144-LS and C135-LS, and subsequently two doses of a SARS-CoV-2 mRNA vaccine. The two antibodies target Class 2 and 3 epitopes that dominate the initial immune response to SARS-CoV-2 infection and mRNA vaccination4-8. Antibody responses to the vaccine in C144-LS and C135-LS recipients produced plasma antigen binding and neutralizing titers that were fractionally lower but not statistically different to controls. In contrast, memory B cells enumerated by flow cytometry after the second vaccine dose were present in higher numbers than in controls. However, the memory B cells that developed in antibody recipients differed from controls in that they were not enriched in VH3-53, VH1-46 and VH3-66 genes and predominantly expressed low-affinity IgM antibodies that carried small numbers of somatic mutations. These antibodies showed altered RBD target specificity consistent with epitope masking, and only 1 out of 77 anti-RBD memory antibodies tested neutralized the virus. The results indicate that pre-existing high-affinity antibodies bias memory B cell selection and have a profound effect on the development of immunological memory in humans that may in part explain the shifting target profile of memory antibodies elicited by the 3rd mRNA vaccine dose.
cc_by_nd
Full text:
1
Collection:
09-preprints
Database:
PREPRINT-MEDRXIV
Language:
En
Year:
2022
Document type:
Preprint