Burnet Institute, Melbourne, Australia.
Department of Immunology and Pathology, Monash University, Melbourne, Australia.
J Infect Dis. 2021 Oct 13;224(7):1128-1138. doi: 10.1093/infdis/jiaa144.
RTS,S is the leading malaria vaccine candidate but only confers partial efficacy against malaria in children. RTS,S is based on the major Plasmodium falciparum sporozoite surface antigen, circumsporozoite protein (CSP). The induction of anti-CSP antibodies is important for protection; however, it is unclear how these protective antibodies function.
We quantified the induction of functional anti-CSP antibody responses in healthy malaria-naive adults (N = 45) vaccinated with RTS,S/AS01. This included the ability to mediate effector functions via the fragment crystallizable (Fc) region, such as interacting with human complement proteins and Fcγ-receptors (FcγRs) that are expressed on immune cells, which promote various immunological functions.
Our major findings were (1) RTS,S-induced antibodies mediated Fc-dependent effector functions, (2) functional antibodies were generally highest after the second vaccine dose, (3) functional antibodies targeted multiple regions of CSP, (4) participants with higher levels of functional antibodies had a reduced probability of developing parasitemia following homologous challenge (P < .05), and (5) nonprotected subjects had higher levels of anti-CSP IgM.
Our data suggest a role for Fc-dependent antibody effector functions in RTS,S-induced immunity. Enhancing the induction of these functional activities may be a strategy to improve the protective efficacy of RTS,S or other malaria vaccines.
NCT00075049.
RTS,S 是领先的疟疾疫苗候选者，但仅对儿童疟疾提供部分疗效。RTS,S 基于主要的恶性疟原虫裂殖子表面抗原环子孢子蛋白（CSP）。诱导抗 CSP 抗体对于保护至关重要；然而，这些保护性抗体如何发挥作用尚不清楚。
我们定量测定了 45 名健康无疟疾的成年参与者接种 RTS,S/AS01 后对功能性抗 CSP 抗体应答的诱导情况。这包括通过片段可结晶（Fc）区域介导效应功能的能力，例如与人补体蛋白相互作用以及表达在免疫细胞上的 Fcγ-受体（FcγRs），这些受体促进各种免疫功能。
我们的主要发现是：（1）RTS,S 诱导的抗体介导 Fc 依赖性效应功能；（2）功能性抗体通常在第二剂疫苗后最高；（3）功能性抗体针对 CSP 的多个区域；（4）具有更高水平功能性抗体的参与者在同源性挑战后发生寄生虫血症的概率降低（P<.05）；（5）未受保护的个体具有更高水平的抗 CSP IgM。
我们的数据表明 Fc 依赖性抗体效应功能在 RTS,S 诱导的免疫中发挥作用。增强这些功能性活动的诱导可能是提高 RTS,S 或其他疟疾疫苗保护效力的一种策略。
NCT00075049。
