Antibody gene features associated with binding and functional activity in malaria vaccine-derived human mAbs

与疟疾疫苗衍生的人类 mAb 的结合和功能活性相关的抗体基因特征

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作者:Camila H Coelho, Susanna Marquez, Bergeline C Nguemwo Tentokam, Anne D Berhe, Kazutoyo Miura, Vishal N Rao, Carole A Long, Ogobara K Doumbo, Issaka Sagara, Sara Healy, Steven H Kleinstein, Patrick E Duffy

Abstract

The impact of adjuvants on malaria vaccine-induced antibody repertoire is poorly understood. Here, we characterize the impact of two adjuvants, Alhydrogel® and AS01, on antibody clonotype diversity, binding and function, post malaria vaccination. We expressed 132 recombinant anti-Pfs230D1 human monoclonal antibodies (mAbs) from participants immunized with malaria transmission-blocking vaccine Pfs230D1, formulated with either Alhydrogel® or AS01. Anti-Pfs230D1 mAbs generated by Alhydrogel® formulation showed higher binding frequency to Pfs230D1 compared to AS01 formulation, although the frequency of functional mAbs was similar between adjuvant groups. Overall, the AS01 formulation induced anti-Pfs230D1 functional antibodies from a broader array of germline sequences versus the Alhydrogel® formulation. All mAbs using IGHV1-69 gene from the Alhydrogel® cohort bound to recombinant Pfs230D1, but did not block parasite transmission to mosquitoes, similar to the IGHV1-69 mAbs isolated from the AS01 cohort. These findings may help inform vaccine design and adjuvant selection for immunization with Plasmodium antigens.

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