Defining functional humoral correlates of immunity to guide vaccine design

定义免疫的功能性体液相关性以指导疫苗设计

• 批准号: 10307582
• 负责人: Facundo Damian Batista
• 金额: $ 80.01万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-11-24 至 2025-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10307582
• 关键词: Affinity; African; Antibodies; Antibody Formation; Antibody-mediated protection; Antigen Targeting; Antigens; Antimalarials; Beds; Binding; Blood group antigen S; Cells; Cellular Immunity; Cessation of life; Child; Clinical; Complement; Complement Receptor; Complex; Data; Development; Disease; Dissection; Drug resistance; Effector Cell; Fc Receptor; Hepatic; Human; Immune; Immune response; Immunity; Immunization; In Vitro; Individual; Infant; Infection; Infection prevention; Innate Immune System; Insecticides; Knowledge; Liver; Malaria; Malaria Vaccines; Masks; Mediating; Modeling; Mosquito Control; Mosquito-borne infectious disease; Natural Killer Cells; Nature; Parasite resistance; Parasites; Persons; Phagocytosis; Plasmodium; Plasmodium falciparum vaccine; Play; Risk; Role; Sampling; Serology; Shapes; Specificity; Sporozoites; System; Vaccination; Vaccine Design; Vaccinee; Vaccines; antimicrobial; design; disorder risk; drug distribution; efficacy study; field study; follow-up; insight; macrophage; malaria infection; mortality; neutrophil; next generation; novel; novel vaccines; pathogen; phase II trial; phase III trial; programs; recruit; response; vaccine development; vaccine evaluation; vaccine platform; vaccine response; vaccine trial; vaccine-induced immunity

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.

疟疾是一种由疟原虫属引起的蚊媒疾病，导致近 50 万人死亡 2017 年，又有 32 亿人面临疾病风险。虽然经过强力杀虫剂处理的蚊帐 分发、蚊虫控制和抗疟疾药物分发计划显着降低了死亡率 与该疾病相关，该疾病继续传播几乎有增无减，这表明针对该疾病的疫苗 迫切需要这种感染。尽管疟疾疫苗设计进展缓慢，但几种疫苗已经 在现场疗效或 2 期试验中显示出 30-50% 的保护效果。相关性 分析表明，体液免疫反应和细胞免疫可能都发挥着关键作用 防止感染；然而，这些免疫反应协同作用的精确机制 驱动免疫可能会为推进下一代疫苗的设计提供重要的见解，从而能够提供 更高水平的全球保护。此外，实地研究强调了潜在的有害影响 流行地区预先存在的抗体对疫苗反应的影响。因此，根据该提案，我们寻求利用 我们的系统血清学抗体分析方法涵盖大量子孢子/早期肝抗原， 定义 PfSPZ 免疫接种后抗疟疾感染的免疫力的相关性以及定义 预先存在的抗体影响疫苗接种反应的具体机制。最终， 这项研究的结果将为开发下一代疟疾疫苗提供新的见解。