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: 10518401
• 负责人: Facundo Damian Batista
• 金额: $ 79.53万
• 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/10518401
• 关键词: Affinity; African; Antibodies; Antibody Formation; Antibody-mediated protection; Antigen Targeting; Antigens; Antimalarials; 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; Macrophage; Malaria; Malaria Vaccines; Mediating; Modeling; Monoclonal Antibodies; Mosquito Control; Mosquito-borne infectious disease; Natural Killer Cells; Nature; Parasite resistance; Parasites; Pattern; Phagocytosis; Plasmodium; Play; Populations at Risk; Role; Sampling; Serology; Shapes; Specificity; Sporozoite vaccine; Sporozoites; System; Vaccination; Vaccine Design; Vaccinee; Vaccines; antimicrobial; design; disorder risk; drug distribution; efficacy study; field study; follow-up; insight; malaria infection; mortality; neutrophil; next generation; novel; novel vaccines; pathogen; phase II trial; phase III trial; programs; recruit; response; synergism; 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。