Defining functional humoral correlates of immunity to guide vaccine design

疟疾是一种由疟疾引起的蚊子传播的疾病，造成近50万人死亡 2017年，又有32亿人面临疾病风险。而攻击性杀虫剂处理过的蚊帐 分发、蚊子控制和抗疟疾药物分发计划显著降低了死亡率 与这种疾病相关的是，这种疾病继续传播，几乎有增无减，这表明疫苗可以预防 这种感染是迫切需要的。尽管疟疾疫苗设计的步伐缓慢，但有几种疫苗已经 在现场表现出希望，在现场药效或第二阶段试验中表现出30%-50%的保护作用。关联性 分析表明，体液免疫反应和细胞免疫都可能起到关键作用。 然而，这些免疫反应协同作用的确切机制是 驾驶免疫可能为推进下一代疫苗的设计提供关键的见解，该疫苗能够提供 更高水平的全球保护。此外，实地研究已经强调了潜在的有害影响 流行区现有抗体对疫苗反应的影响。因此，在这项提议下，我们试图利用 我们的系统血清学抗体谱方法，跨大量的子孢子/早期肝脏抗原，以 定义接种PfSPZ后对疟疾感染的免疫相关因素以及定义 预先存在的抗体塑造对疫苗接种反应的特定机制(S)。归根结底， 这项研究的结果将为开发下一代疟疾疫苗提供新的见解。

Malaria, a mosquito-borne disease caused by Plasmodium spp., was responsible for nearly half a million deaths in 2017, with an additional 3.2 billion people at risk of disease. While aggressive insecticide-treated bed-net distribution, mosquito control, and anti-malarial drug distribution programs have significantly reduced mortality associated with the disease, the disease continues to spread nearly unabated, suggesting that a vaccine against this infection is desperately needed. Despite the slow pace of malaria vaccine design, several vaccines have shown promise in the field demonstrating 30–50% protection in field efficacy or Phase 2 trials. Correlates analyses have suggested that both humoral immune responses and cellular immunity may both play critical parts in protection from infection; however, the precise mechanism by which these immune responses synergize to drive immunity may provide the critical insights to advance the design of next-generation vaccines able to provide higher levels of global protection. Moreover, field studies have highlighted the potentially deleterious influence of pre-existing antibodies in endemic regions on vaccine response. Thus, under this proposal we seek to exploit our Systems Serology antibody profiling approach, across a large array of sporozoite/early liver antigens, to define both the correlates of immunity against malaria infection following PfSPZ immunization as well as to define the specific mechanism(s) by which pre-existing antibodies shape the response to vaccination. Ultimately, the results from this study will provide novel insights for the development of next generation vaccines against malaria.