Detailed mapping and analysis of the evolution of neutralizing antibody responses

大多数患有慢性HIV感染的人都会经历免疫系统的严重失调。长寿命记忆B细胞消失，而未成熟的B细胞被过度激活并产生大量无效的免疫球蛋白。此外，CD4细胞，HIV的主要目标，在感染的慢性阶段稳步下降。大约10-20%的艾滋病毒感染者克服或摆脱了这种广泛的免疫功能障碍，并产生广泛中和的艾滋病毒抗体。了解这些个体如何产生广泛中和的艾滋病毒抗体对艾滋病毒疫苗的开发至关重要。

Most individuals with chronic HIV infection experience massive dysregulation of the immune system. Longlived memory B cells disappear, while immature B cells are hyperactivated and produce significant quantities of ineffective immunoglobulin. Furthermore, CD4 cells, the primary targets of HIV, steadily decline during the chronic phase of infection. Approximately 10-20% of HIV infected individuals overcome or escape this widespread immune dysfunction and produce broadly neutralizing antibodies to HIV. An understanding of how these indivduals generate broadly neutralizing antibodies to HIV is critical for HIV vaccine development. We hypothesize that H1V+ elite neutralizers have a less disrupted B lymphocyte compartment and/or an enhanced population of follicular helper CD4 T lymphocytes when compared to average or poorly neutralizing individuals. This hypothesis will be tested by multiparameter flow cytometric analysis of B and T lymphocyte populations at two early and two late time points post-infection, comparing indivuals who generate broadly neutralizing antibodies with average/poor neutralizers and uninfected individuals. The ability of B lymphocytes to differentiate into antibody secreting cells and the capacity of follicular T helper CD4 cells to produce important helper cytokines, such as IL-4 and IL-21, will also be compared in elite and poorly neutralizing individuals. These findings will help determine how elite neutralizers generate useful antibodies to HIV, and could greatly assist in the development of an effective HIV vaccine.