Conversion of vaccines from low to high immunogenicity by antibodies with epitope complementarity.

Autor:	Dvorscek AR; Department of Immunology, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia., McKenzie CI; Department of Immunology, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia., Stäheli VC; Department of Immunology, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia., Ding Z; Department of Immunology, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia., White J; Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, NSW 2010, Australia., Fabb SA; Monash Institute of Pharmaceutical Sciences, Monash University, 399 Royal Parade, Parkville, VIC 3052, Australia., Lim L; Monash Institute of Pharmaceutical Sciences, Monash University, 399 Royal Parade, Parkville, VIC 3052, Australia., O'Donnell K; Department of Immunology, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia., Pitt C; Department of Immunology, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia., Christ D; Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, NSW 2010, Australia., Hill DL; Department of Immunology, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia., Pouton CW; Monash Institute of Pharmaceutical Sciences, Monash University, 399 Royal Parade, Parkville, VIC 3052, Australia., Burnett DL; Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; School of Biomedical Sciences, University of New South Wales, Sydney, NSW 2010, Australia., Brink R; Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, NSW 2010, Australia., Robinson MJ; Department of Immunology, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia., Tarlinton DM; Department of Immunology, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia., Quast I; Department of Immunology, Monash University, 89 Commercial Rd, Melbourne, VIC 3004, Australia. Electronic address: isaak.quast@monash.edu.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2024 Oct 08; Vol. 57 (10), pp. 2433-2452.e7. Date of Electronic Publication: 2024 Sep 20.
DOI:	10.1016/j.immuni.2024.08.017
Abstrakt:	Existing antibodies (Abs) have varied effects on humoral immunity during subsequent infections. Here, we leveraged in vivo systems that allow precise control of antigen-specific Abs and B cells to examine the impact of Ab dose, affinity, and specificity in directing B cell activation and differentiation. Abs competing with the B cell receptor (BCR) epitope showed affinity-dependent suppression. By contrast, Abs targeting a complementary epitope, not overlapping with the BCR, shifted B cell differentiation toward Ab-secreting cells. Such Abs allowed for potent germinal center (GC) responses to otherwise poorly immunogenic sites by promoting antigen capture and presentation by low-affinity B cells. These mechanisms jointly diversified the B cell repertoire by facilitating the recruitment of high- and low-affinity B cells into Ab-secreting cell, GC, and memory B cell fates. Incorporation of small amounts of monoclonal Abs into protein- or mRNA-based vaccines enhanced immunogenicity and facilitated sustained immune responses, with implications for vaccine design and our understanding of protective immunity. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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