B cell-intrinsic TLR7 signaling is required for neutralizing antibody responses to SARS-CoV-2 and pathogen-like COVID-19 vaccines

Eur J Immunol. 2023 Jul 12:e2350437. doi: 10.1002/eji.202350437. Online ahead of print.ABSTRACTToll-like receptor 7 (TLR7) triggers antiviral immune responses through its capacity to recognize single-stranded RNA. TLR7 loss-of-function mutants are associated with life-threatening pneumonia in severe COVID-19 patients. Whereas TLR7-driven innate induction of type I IFN appears central to control SARS-CoV2 virus spreading during the first days of infection, the impact of TLR7-deficiency on adaptive B-cell immunity is less clear. In the present study, we examined the role of TLR7 in the adaptive B cells response to various pathogen-like antigens (PLAs). We used inactivated SARS-CoV2 and a PLA-based COVID-19 vaccine candidate designed to mimic SARS-CoV2 with encapsulated bacterial ssRNA as TLR7 ligands and conjugated with the RBD of the SARS-CoV2 Spike protein. Upon repeated immunization with inactivated SARS-CoV2 or PLA COVID-19 vaccine, we show that Tlr7-deficiency abolished the germinal center (GC)-dependent production of RBD-specific class-switched IgG2b and IgG2c, and neutralizing antibodies to SARS-CoV2. We also provide evidence for a non-redundant role for B-cell-intrinsic TLR7 in the promotion of RBD-specific IgG2b/IgG2c and memory B cells. Together, these data demonstrate that the GC reaction and class-switch recombination to the Myd88-dependent IgG2b/IgG2c in response to SARS-CoV2 or PLAs is strictly dependent on cell-intrinsic activation of TLR7 in B cells.PMID:3743897...
Source: European Journal of Immunology - Category: Allergy & Immunology Authors: Source Type: research