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

IF 25.5 1区 医学 Q1 IMMUNOLOGY Immunity Pub Date : 2024-09-20 DOI:10.1016/j.immuni.2024.08.017
Alexandra R. Dvorscek, Craig I. McKenzie, Vera C. Stäheli, Zhoujie Ding, Jacqueline White, Stewart A. Fabb, Leonard Lim, Kristy O’Donnell, Catherine Pitt, Daniel Christ, Danika L. Hill, Colin W. Pouton, Deborah L. Burnett, Robert Brink, Marcus J. Robinson, David M. Tarlinton, Isaak Quast
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Abstract

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.

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通过具有表位互补性的抗体将疫苗从低免疫原性转化为高免疫原性
现有的抗体(Abs)在随后的感染过程中对体液免疫有不同的影响。在这里,我们利用可精确控制抗原特异性抗体和 B 细胞的体内系统,研究了抗体剂量、亲和力和特异性在引导 B 细胞活化和分化方面的影响。与 B 细胞受体 (BCR) 表位竞争的抗体表现出亲和力依赖性抑制。与此相反,以互补表位为靶点、不与BCR重叠的Abs能使B细胞向分泌Abs的细胞分化。通过促进低亲和力 B 细胞对抗原的捕获和呈递,这种抗体能对免疫原性较差的部位产生有效的生殖中心(GC)反应。这些机制通过促进高亲和力和低亲和力 B 细胞招募成为抗体分泌细胞、GC 和记忆 B 细胞,共同实现了 B 细胞谱系的多样化。在基于蛋白质或 mRNA 的疫苗中加入少量单克隆抗体可增强免疫原性并促进持续的免疫应答,这对疫苗设计和我们对保护性免疫的理解都有影响。
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来源期刊
Immunity
Immunity 医学-免疫学
CiteScore
49.40
自引率
2.20%
发文量
205
审稿时长
6 months
期刊介绍: Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.
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