In the B Cell Focus our overall goals are to 1) design Env immunogens that will elicit both difficult-to-induce broad neutralizing antibodies, and also 2) induce easier-to-induce protective antibodies. The goal is to induce both types of antibodies in most vaccinated subjects.
Specific aims i nclude:
Aim 1. To define the nature of protective systemic and mucosal immunity in vaccinated subjects.
Aim 2. To design novel gp120/gp140 immunogens that induces protective mucosal and systemic antibody responses to HlV-1.
Aim 3. To define host factors that may limit the induction of broadly neutralizing antibodies.
Aim 4. To design immunogens that target unmutated ancestor and intermediate antibodies of the maturation pathways of protective anti-HlV-1 Env antibodies.
Aim 5. To use structural biological information and technology to design immunogens. Thus, the B Cell Focus will use recombinant monoclonal antibody technology to study unique mucosal samples from those vaccinated with current vaccines;will work to define the types of antibodies and their protective nature induced at mucosal sites (Aim 1);will test new, more antigenic and immunogenic transmitted/founder Env immunogens in Aim 2, will determine tolerance and other immunoregulatory host factors that control induction of difficult-to-induce broadly neutralizing antibodies (BnAbs) (Aim 3);will isolate clonal lineages of BnAbs to define precursor antibodies to use as templates upon which to design new immunogens for driving unusual or complex maturation pathways (Aim 4), and will solve the near atomic resolution structure of the membrane associated trimer by cryoEM for rationale vaccine design (Aim 5). The work of the B Cell Focus builds on discoveries made over the past 6 years in CHAVI, and aims to overcome the current roadblocks preventing inducing protective antibodies in the majority of vaccinated subjects.
Characterization of the antibody specificities in the settings of vaccination and those rare infected people who make desired antibody responses will allow a better understanding of the easy vs. harder to induce protective antibodies and will aid in the design of immunogens that induce antibody responses that effectively prevent HIV transmission regardless of the portal of entry.
|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