ABSTRACT
mRNA-based vaccines provide effective protection against most common SARS-CoV-2 variants. However, identifying likely breakthrough variants is critical for future vaccine development. Here, we found that the Delta variant completely escaped from anti-N-terminal domain (NTD) neutralizing antibodies, while increasing responsiveness to anti-NTD infectivity-enhancing antibodies. Although Pfizer-BioNTech BNT162b2-immune sera neutralized the Delta variant, when four common mutations were introduced into the receptor binding domain (RBD) of the Delta variant (Delta 4+), some BNT162b2-immune sera lost neutralizing activity and enhanced the infectivity. Unique mutations in the Delta NTD were involved in the enhanced infectivity by the BNT162b2-immune sera. Sera of mice immunized by Delta spike, but not wild-type spike, consistently neutralized the Delta 4+ variant without enhancing infectivity. Given the fact that a Delta variant with three similar RBD mutations has already emerged according to the GISAID database, it is necessary to develop vaccines that protect against such complete breakthrough variants.
ABSTRACT
Objective:To investigate the role of B cell adoptor protein with ankyrin repeats ( BANK ) in experimental autoimmune encephalomyelitis ( EAE) .Methods: C57BL/6 mice and BANK-deficient ( BANK-/-) mice were immunized with MOG peptide in CFA,and then observed the clinical symptoms and pathological severity .Results: The percentages of CD4+T cells,CD8+T cells and regulatory T cells in brain and spleen were analyzed by flow cytometry .BANK-/-mice showed significantly higher score at the peak and the plateau phase compared with wild-type mice(P<0.05).HE staining showed more widespread areas of inflammation and demyelination in BANK-/-mice when compared to wild-type mice on day 16.In addition,the frequency of CNS-infiltrating CD8+T cells was markedly higher in BANK-/-mice than in wild-type mice.In addition,the percentage of CD8+T cells from spleen in BANK-/-mice was also increased compared with wild-type mice (P<0.05).By contrast,the percentage of regulatory T cells and the ratio of CD 4/CD8 T cells from spleen in BANK-/-mice were significantly lower than in wild-type mice(P<0.05).Conclusion:Thus,BANK expression in B cells can inhibit the development of EAE .
