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.
|Chen, Jia; Frey, Gary; Peng, Hanqin et al. (2014) Mechanism of HIV-1 neutralization by antibodies targeting a membrane-proximal region of gp41. J Virol 88:1249-58|
|Hraber, Peter; Seaman, Michael S; Bailer, Robert T et al. (2014) Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection. AIDS 28:163-9|
|Pollara, Justin; Bonsignori, Mattia; Moody, M Anthony et al. (2014) HIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activities. J Virol 88:7715-26|
|Verkoczy, Laurent; Diaz, Marilyn (2014) Autoreactivity in HIV-1 broadly neutralizing antibodies: implications for their function and induction by vaccination. Curr Opin HIV AIDS 9:224-34|
|Hwang, Kwan-Ki; Trama, Ashley M; Kozink, Daniel M et al. (2014) IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria. PLoS One 9:e90725|
|Haynes, Barton F; Moody, M Anthony; Alam, Munir et al. (2014) Progress in HIV-1 vaccine development. J Allergy Clin Immunol 134:3-10; quiz 11|
|Holl, T Matt; Yang, Guang; Kuraoka, Masayuki et al. (2014) Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes. J Immunol 192:3269-79|
|Roederer, Mario; Keele, Brandon F; Schmidt, Stephen D et al. (2014) Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV. Nature 505:502-8|
|Dennison, S Moses; Anasti, Kara M; Jaeger, Frederick H et al. (2014) Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose a CD4-inducible epitope and block the interaction of HIV-1 gp140 with galactosylceramide. J Virol 88:9406-17|
|Fera, Daniela; Schmidt, Aaron G; Haynes, Barton F et al. (2014) Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains. Proc Natl Acad Sci U S A 111:10275-80|
Showing the most recent 10 out of 48 publications