Inducing long-lasting HIV Env-specific antibody responses by intrastructural help
Research has shown that attempts to vaccinate against HIV have resulted in inefficient and waning protection. One reason for this is the inability of candidate vaccines to mount an efficient humoral immune response. Humoral immunity depends on production of antibodies, which need to be able to fight the virus and to remain viable in the body for months and years. Inefficiency of antibodies is often due to a suboptimal ability to trigger immune functions that would otherwise remove infected cells and circulating pathogens. It is postulated that production of persistent and functional antibody titres is dependent on efficient help by T cells. In this regard, intrastructural help (ISH) might be a promising approach to modulate the humoral response through the aid of T cell immunity. Recent research on mice has shown that it is possible to increase the antibody response against virus-like particles (VLPs) bearing HIV Env on their surface and that contain proteins in their core used to harness the help of T cells. The long-term goal of this project is to develop a vaccine strategy able to trigger a strong and long-lasting humoral response against HIV Env through ISH. To do so, I will identify immunodominant epitopes for optimal T helper cell responses and incorporate them into VLPs as core constituents. I will then immunize mice with VLPs expressing HIV Env on their surface and the immunodominant epitopes in their core. Ultimately, the humoral response in these mice will be characterised by assessing the functionality of the antibody produced as well as the type of B cells generated. Fc effector functions, IgG isotyping, and glycan profile screening will define antibody functionality; whereas, presence of long-lived plasma cells and memory B cells will be characteristic of long-lasting immunity. Production of functional antibodies and memory cells would further corroborate the ability of ISH to modulate the humoral response and could perhaps pave the way to a new strategy for vaccine development not only against HIV.
