A vaccine for HIV is a global health priority. Efforts to develop a successful HIV vaccine using standard immune responses have so far failed. Lateral thinking is required to explore novel phenomena in HIV-specific immunity. The cytotoxic capacity of natural killer (NK) cells provides one such opportunity to open up a new horizon that could eventually be utilised in rational vaccine design. Antibody dependent cell mediated cytotoxicity (ADCC) allows for antigen-specific targeting of NK cell activity. Previous studies of the role of ADCC activity in HIV infection have been hampered by difficulties identifying and mapping these responses. We developed a novel technique to detected HIV peptide-specific antibody dependent cell mediated cytotoxicity (ADCC) mediated by NK cells in HIV positive individuals. The technique allows for rapid detection and quantification of cytokine expression by NK-cells mediated through ADCC on small volumes of blood or plasma;it also allows for mapping precise epitopes targeted by these responses. We now wish to exploit this technology to determine the biological significance of HIV-specific ADCC responses and use this knowledge to develop potentially effective HIV vaccines.

Public Health Relevance

Novel approaches are required to determine how best to induce immunity to HIV. HIV is causing a devastating pandemic and it is widely believed that a vaccine will be essential to ultimately slowing this pandemic. This project is studying a novel immune response called ADCC which we believe may be a useful component of immunity to HIV.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI081541-01A2
Application #
7836875
Study Section
HIV/AIDS Vaccines Study Section (VACC)
Program Officer
Shapiro, Stuart Z
Project Start
2010-04-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
1
Fiscal Year
2010
Total Cost
$148,500
Indirect Cost
Name
University of Melbourne
Department
Type
DUNS #
753575117
City
Melbourne
State
Country
Australia
Zip Code
3010
Madhavi, Vijaya; Navis, Marjon; Chung, Amy W et al. (2013) Activation of NK cells by HIV-specific ADCC antibodies: role for granulocytes in expressing HIV-1 peptide epitopes. Hum Vaccin Immunother 9:1011-8
Wren, Leia H; Chung, Amy W; Isitman, Gamze et al. (2013) Specific antibody-dependent cellular cytotoxicity responses associated with slow progression of HIV infection. Immunology 138:116-23
Kramski, M; Schorcht, A; Johnston, A P R et al. (2012) Role of monocytes in mediating HIV-specific antibody-dependent cellular cytotoxicity. J Immunol Methods 384:51-61
Wren, Leia; Parsons, Matthew S; Isitman, Gamze et al. (2012) Influence of cytokines on HIV-specific antibody-dependent cellular cytotoxicity activation profile of natural killer cells. PLoS One 7:e38580
Parsons, Matthew S; Wren, Leia; Isitman, Gamze et al. (2012) HIV infection abrogates the functional advantage of natural killer cells educated through KIR3DL1/HLA-Bw4 interactions to mediate anti-HIV antibody-dependent cellular cytotoxicity. J Virol 86:4488-95
Isitman, Gamze; Chung, Amy W; Navis, Marjon et al. (2011) Pol as a target for antibody dependent cellular cytotoxicity responses in HIV-1 infection. Virology 412:110-6
Chung, Amy W; Isitman, Gamze; Navis, Marjon et al. (2011) Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure. Proc Natl Acad Sci U S A 108:7505-10
Chung, Amy W; Navis, Marjon; Isitman, Gamze et al. (2011) Activation of NK cells by ADCC antibodies and HIV disease progression. J Acquir Immune Defic Syndr 58:127-31
Chung, Amy W; Navis, Marjon; Isitman, Gamze et al. (2011) Activation of NK cells by ADCC responses during early HIV infection. Viral Immunol 24:171-5
Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Ganguly, Nirmal et al. (2010) Defining the objectives of the AIDS vaccine for Asia network: report of the WHO-UNAIDS/Global HIV vaccine enterprise regional consultation on expanding AIDS vaccine research and development capacity in Asia. Curr Opin HIV AIDS 5:435-52