東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

DNA vaccines for immunotherapy of HIV.

Fuller, Deborah Heydenburg.

Linked to FindBook

Google Book

Amazon

博客來

DNA vaccines for immunotherapy of HIV.

Record Type:	Electronic resources : Monograph/item
Title/Author:	DNA vaccines for immunotherapy of HIV./
Author:	Fuller, Deborah Heydenburg.
Description:	163 p.
Notes:	Source: Dissertation Abstracts International, Volume: 63-04, Section: B, page: 1773.
Contained By:	Dissertation Abstracts International63-04B.
Subject:	Health Sciences, Immunology. -
Online resource:	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.
LDR:03344nmm 2200289 4500 001 1855742
005 20040629073630.5
008 130614s2001 eng d
020 $a 0493639071
035 $a (UnM)AAI3049361
035 $a AAI3049361
040 $a UnM $c UnM
100 1 $a Fuller, Deborah Heydenburg. $3 1943543
245 1 0 $a DNA vaccines for immunotherapy of HIV.
300 $a 163 p.
500 $a Source: Dissertation Abstracts International, Volume: 63-04, Section: B, page: 1773.
500 $a Supervisor: David I. Watkins.
502 $a Thesis (Ph.D.)--The University of Wisconsin - Madison, 2001.
520 $a 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.
590 $a School code: 0262.
650 4 $a Health Sciences, Immunology. $3 1017716
650 4 $a Health Sciences, Pathology. $3 1017854
650 4 $a Biology, Molecular. $3 1017719
690 $a 0982
690 $a 0571
690 $a 0307
710 2 0 $a The University of Wisconsin - Madison. $3 626640
773 0 $t Dissertation Abstracts International $g 63-04B.
790 1 0 $a Watkins, David I., $e advisor
790 $a 0262
791 $a Ph.D.
792 $a 2001
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3049361