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DNA vaccines for immunotherapy of HIV.

Fuller, Deborah Heydenburg.

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DNA vaccines for immunotherapy of HIV.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	DNA vaccines for immunotherapy of HIV./
作者:	Fuller, Deborah Heydenburg.
面頁冊數:	163 p.
附註:	Source: Dissertation Abstracts International, Volume: 63-04, Section: B, page: 1773.
Contained By:	Dissertation Abstracts International63-04B.
標題:	Health Sciences, Immunology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3049361
ISBN:	0493639071

DNA vaccines for immunotherapy of HIV.
Fuller, Deborah Heydenburg.

DNA vaccines for immunotherapy of HIV. - 163 p.

Source: Dissertation Abstracts International, Volume: 63-04, Section: B, page: 1773.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2001.

Immunization with vaccines that induce HIV-specific CTL during highly active anti-retroviral therapy (HAART) offers a viable strategy for immunotherapy against HIV. Toward that end, we designed a novel DNA vaccine to optimize induction of CTL. DNA vaccines encoding epitopes fused to a carrier gene encoding hepatitis B core antigen induced significantly higher levels of CTL in mice than DNA vaccines encoding whole genes or epitopes in the absence of carrier. This strategy also induced broad CTL responses to multiple epitopes in rhesus macaques. Since vaccine induction of virus-specific CD4+ T helper (Th) cell responses may be critical for recall of virus-specific CTL, we investigated the role of virus-specific Th responses in CTL recall. Mice were primed for HIV-specific CTL in the context of either HIV-specific or non-specific HBcAg Th responses. The CD8+ T cell recall response was then monitored after challenging with a recombinant HIV-vaccinia. We observed that HIV-specific Th responses were essential to maintain the HIV-specific CD8+ effector T cell recall function and protect from challenge, documenting a critical role for the virus-specific Th cell subset in the maintenance of virus-specific CTL. The HBcAg-epitope DNA vaccine approach in combination with the DNA vaccines encoding SIVgag and tat were then tested as adjunct immunotherapy to HAART in SIV-infected rhesus macaques. Forty macaques were infected with a primary SIV isolate and then vaccinated using the PowderJect<super>®</super> delivery device. One group of animals was vaccinated post-infection and initiation of therapy with the anti-retroviral drug PMPA ([R]-9-[2-phosphonylmethoxypropyl] adenine). A second group was vaccinated both prior to and post-infection and initiation of therapy with PMPA. Vaccine-primed animals exhibited augmented SIV-specific T cell responses and suppression of viremia during anti-retroviral therapy. Following suspension of drug therapy, virus rebounded in all 8 controls. In contrast, significant containment was observed in 7 of 16 vaccine-primed macaques and 3 of 16 macaques vaccinated only post-infection, suggesting that vaccination prior to infection enhances the effectiveness of post-infection immunotherapy. These results document the first evidence that therapeutic vaccination can induce a measurable impact on viral burden in AIDS infection and support further development of DNA vaccines for immunotherapy of HIV.

ISBN: 0493639071Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

DNA vaccines for immunotherapy of HIV.
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