The induction of both CD4+ and CD8+ T cell responses will be of central importance for vaccine protection against HIV-1. However, a number of major questions must be answered before a vaccine can be developed that optimizes these immune responses. While we know that an optimal vaccine-induced antibody response will require CD4+ T cell help, the nature of the help that will potentiate the highest titer and most durable antibody response remains unclear. Although CD8+ T cells have been shown to contribute to containment of HIV-1 replication, the effectiveness of this anti-viral response is limited by the extreme sequence variability of circulating HIV-1 strains and the propensity of the virus to mutate away from recognition by these effector cells. Truly effective CD8+ T cell containment of HIV-1 replication can only occur if T cell responses are generated through vaccination that can pre-empt the ability of the virus to escape from cellular immune recognition. The studies described in this focus address these central issues in HIV-1 vaccine development.
Specific Aims are as follows.
Aim 1. Evaluate different priming vectors for their ability to stimulate CD4+ Th2 cells and T follicular helper (Tfh) cells in macaques.
Aim 2. Characterize CD4+ Th2 cell and Tfh cell responses elicited by HIV-1 vaccines in humans Aim 3. Determine impact of naive repertoires on post-vaccination response of HIV-1 Env-specific CD4+T cells in humans.
Aim 4. Compare mosaic and conserved region vaccines for their induction of CD8+ T cell responses.
Aim 5. Apply new understanding of immunodominance to improve vaccine-elicited CD8+ T cell responses. The information gained in addressing these aims will lead directly to the design of the next generation of vaccines that will stimulate more protective CD4+ T cell and CD8+ T cell responses.
An effective HIV vaccine will have to stimulate long lasting antibody response and cellular (T cell) immune responses. Two types of T cells are important, CD4+ T cells that help B cells to generated effective antibody and CD8+ T cells that act directly on virus infected cells. This focus will find new ways to generate both.
|Pollara, Justin; Easterhoff, David; Fouda, Genevieve G (2017) Lessons learned from human HIV vaccine trials. Curr Opin HIV AIDS 12:216-221|
|Arakelyan, Anush; Fitzgerald, Wendy; King, Deborah F et al. (2017) Flow virometry analysis of envelope glycoprotein conformations on individual HIV virions. Sci Rep 7:948|
|Go, Eden P; Ding, Haitao; Zhang, Shijian et al. (2017) Glycosylation Benchmark Profile for HIV-1 Envelope Glycoprotein Production Based on Eleven Env Trimers. J Virol 91:|
|Verkoczy, Laurent; Alt, Frederick W; Tian, Ming (2017) Human Ig knockin mice to study the development and regulation of HIV-1 broadly neutralizing antibodies. Immunol Rev 275:89-107|
|Haynes, Barton F; Mascola, John R (2017) The quest for an antibody-based HIV vaccine. Immunol Rev 275:5-10|
|Bonsignori, Mattia; Liao, Hua-Xin; Gao, Feng et al. (2017) Antibody-virus co-evolution in HIV infection: paths for HIV vaccine development. Immunol Rev 275:145-160|
|Kelsoe, Garnett; Haynes, Barton F (2017) What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Breaking through Immunity's Glass Ceiling. Cold Spring Harb Perspect Biol :|
|Herschhorn, Alon; Sodroski, Joseph (2017) An entry-competent intermediate state of the HIV-1 envelope glycoproteins. Receptors Clin Investig 4:|
|Ding, Shilei; Verly, Myriam M; Princiotto, Amy et al. (2017) Short Communication: Small-Molecule CD4 Mimetics Sensitize HIV-1-Infected Cells to Antibody-Dependent Cellular Cytotoxicity by Antibodies Elicited by Multiple Envelope Glycoprotein Immunogens in Nonhuman Primates. AIDS Res Hum Retroviruses 33:428-431|
|Espy, Nicole; Pacheco, Beatriz; Sodroski, Joseph (2017) Adaptation of HIV-1 to cells with low expression of the CCR5 coreceptor. Virology 508:90-107|
Showing the most recent 10 out of 220 publications