Coelho Camila H, Marquez Susanna, Nguemwo Tentokam Bergeline C, Berhe Anne D, Miura Kazutoyo, Rao Vishal N, Long Carole A, Doumbo Ogobara K, Sagara Issaka, Healy Sara, Kleinstein Steven H, Duffy Patrick E
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
NPJ Vaccines. 2024 Aug 10;9(1):144. doi: 10.1038/s41541-024-00929-6.
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.
佐剂对疟疾疫苗诱导的抗体库的影响目前了解甚少。在此，我们描述了两种佐剂，即氢氧化铝佐剂（Alhydrogel®）和AS01，在疟疾疫苗接种后对抗体克隆型多样性、结合能力和功能的影响。我们表达了132种重组抗Pfs230D1人单克隆抗体（mAb），这些抗体来自接种了用Alhydrogel®或AS01配制的疟疾传播阻断疫苗Pfs230D1的参与者。与AS01配方相比，Alhydrogel®配方产生的抗Pfs230D1 mAb对Pfs230D1的结合频率更高，尽管佐剂组之间功能性mAb的频率相似。总体而言，与Alhydrogel®配方相比，AS01配方从更广泛的种系序列中诱导出抗Pfs230D1功能性抗体。Alhydrogel®组中所有使用IGHV1-69基因的mAb都与重组Pfs230D1结合，但不能阻断寄生虫向蚊子的传播，这与从AS01组分离出的IGHV1-69 mAb相似。这些发现可能有助于为疟原虫抗原免疫的疫苗设计和佐剂选择提供参考。
