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

基本信息

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
项目类别：
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

项目摘要

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.

疟疾是由疟原虫属引起的蚊子传播疾病，造成近50万人死亡 2017年，有32亿人有疾病风险。而侵略性杀虫剂处理的床网分配，蚊子控制和抗疟疾药物分配计划的死亡率显着降低与疾病相关，该疾病继续传播几乎没有减弱，表明疫苗反对迫切需要这种感染。尽管疟疾疫苗设计的速度缓慢，但几种疫苗仍有在现场显示了有望在现场效率或2期试验中的保护状态显示30–50％。相关分析表明，体液免疫复杂和细胞免疫调查都可能发挥关键作用防止感染；但是，这些免疫反应协同与之协同的确切机制驱动免疫力可能会提供关键的见解，以推动下一代疫苗的设计以提供较高的全球保护水平。此外，现场研究强调了潜在删除的影响疫苗反应中内人体区域中预先存在的抗体的抗体。根据这个建议，我们试图利用我们的系统血清学抗体分析方法，遍布大量的孢子菌/早期肝抗原在PFSPZ免疫后以及定义预先存在的抗体塑造了对疫苗接种反应的特定机制。最终，这项研究的结果将为开发针对疟疾的下一代疫苗的开发提供新的见解。