Our understanding of the biology of the innate immune systems is rapidly expanding. We are gaining an increasing understanding of the receptors expressed by NK cells that specifically mediate the inhibition and activation of these cells, as well as the ligands for these receptors. It is becoming clear that innate immune signals can dramatically modulate adaptive immune response. Emerging data are implicating NK cells and Other innate immune responses in the early control of HIV-1 replication during primary infection. The recent demonstration that it is possible to generate memory responses in the innate immune system raises the possibility that it may be feasible to use vaccines to enhance anti-viral innate immunity to help terminate or control very early HIV-1 infection. We will explore this possibility in the following aims:
Aim 1. Recombinant canary-pox elicited innate responses and their contribution to shaping adaptive immune responses in rhesus monkeys Aim 2. Vaccination with KIR ligands for induction of immunologic memory for innate NK cell responses in rhesus monkeys and humans Aim 3. CD8+ T cell-produced factors and control of viremia The information gained in these studies about the anti-SIV and anti-HIV protective capacity of innate immune responses will lead directly to advances in vaccine design.
Early in acute HIV-1 infection innate immune responses are activated and evidence suggests that they are important in the potential control of the virus. Recent studies suggest a form of virus-induced innate memory. Therefore, it is important to determine if HlV-1 vaccines can induce innate memory to augment protective immune responses to HIV-1 infection.
|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