The worldwide AIDS epidemic is most devastating in developing countries, where mOfe than 40 million people are Infected. Development of an HIV-1 vaccine for POPulations In southern Africa and other developing countries is the highest priority. Currentiy HIV-1 vaccines designed to drive Th1-type and cytotoxic CD8+ T cell fesponses afe the candidate vaccines in development or in clinical trials. In addition, inhabitants in developing countries aTe also infected with helminth parasites which suppress immune responses to ThHype vaccines and expansion of viral antigenspecific C04+ and CDS+ T cell responses. Therefore, how helminth Infection impacts the induction of neutrali;!:;ing antibodies or robust T cell responses to candidate HIV-1 vaccines is an Important question to investigate prior to testing of candidate vaGCill6s in helminth infected populations. In this application we propose to examine immune responses to a gut-deUvered Listeria vector HIV-1 vaccine in naIVe and schIStosome infected mice. We chose Listeria vectors do to the fact that the gut is the ear1y site of HIV-1 replication. In addition to the impact of helminth infection, we will also examine how prior infection and then re -Infectlon with helminth parasites impacts the ability of Listeria vector HIV-1 vaccines to induce neutralizing antibody and vaccine specific T cell responses in mice . . We will also determine if reinfection with schistosomes impacts T cell memory. We also propose 10 examine both of these questions in Th1-type and Th2-type mice.
The specifiC aims of this proposal are: 1) Will eradication of schistosome infection In mice allow their immune systems to mount strong C04+ and CD8+ T celi and neutralizing ab responses follOWing vaccination with Listeria vector HIV?1 candidate vaccines? 2) Will re? lnfection with schistosomes alter Llst~ria vector HIV-1 vaccine induced neutralizing antibody orT cell memory responses?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI071883-02
Application #
7877043
Study Section
HIV/AIDS Vaccines Study Section (VACC)
Program Officer
Mehra, Vijay L
Project Start
2009-06-19
Project End
2011-05-30
Budget Start
2010-06-01
Budget End
2011-05-30
Support Year
2
Fiscal Year
2010
Total Cost
$372,166
Indirect Cost
Name
University of Georgia
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
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Bui, Cac T; Shollenberger, Lisa M; Paterson, Yvonne et al. (2015) Schistosoma mansoni soluble egg antigens enhance T cell responses to a newly identified HIV-1 Gag H-2b epitope. Clin Vaccine Immunol 22:193-9
Bui, Cac T; Shollenberger, Lisa M; Paterson, Yvonne et al. (2014) Schistosoma mansoni soluble egg antigens enhance Listeria monocytogenes vector HIV-1 vaccine induction of cytotoxic T cells. Clin Vaccine Immunol 21:1232-9
Shollenberger, Lisa M; Bui, Cac; Paterson, Yvonne et al. (2013) Successful vaccination of immune suppressed recipients using Listeria vector HIV-1 vaccines in helminth infected mice. Vaccine 31:2050-6
Shollenberger, Lisa M; Bui, Cac T; Paterson, Yvonne et al. (2013) HIV-1 vaccine-specific responses induced by Listeria vector vaccines are maintained in mice subsequently infected with a model helminth parasite, Schistosoma mansoni. Vaccine 31:5651-8