Cytotoxic T Lymphocyte and Antibody Responses Generated in Rhesus Monkeys Immunized with Retroviral Vector-Transduced Fibroblasts Expressing Human Immunodeficiency Virus Type-1 IIIB ENV/REV Proteins

1994 ◽  
Vol 5 (7) ◽  
pp. 853-862 ◽  
Author(s):  
Lisa S. Laube ◽  
Michelle Burrascano ◽  
Cataline E. Dejesus ◽  
Brad D. Howard ◽  
Marlene A. Johnson ◽  
...  
2005 ◽  
Vol 79 (5) ◽  
pp. 2956-2963 ◽  
Author(s):  
Michael S. Seaman ◽  
Ling Xu ◽  
Kristin Beaudry ◽  
Kristi L. Martin ◽  
Margaret H. Beddall ◽  
...  

ABSTRACT The development of a human immunodeficiency virus type 1 (HIV-1) vaccine that elicits potent cellular and humoral immune responses recognizing divergent strains of HIV-1 will be critical for combating the global AIDS epidemic. The present studies were initiated to examine the magnitude and breadth of envelope (Env)-specific T-lymphocyte and antibody responses generated by vaccines containing either a single or multiple genetically distant HIV-1 Env immunogens. Rhesus monkeys were immunized with DNA prime-recombinant adenovirus boost vaccines encoding a Gag-Pol-Nef polyprotein in combination with either a single Env or a mixture of clade-A, clade-B, and clade-C Envs. Monkeys receiving the multiclade Env immunization developed robust immune responses to all vaccine antigens and, importantly, a greater breadth of Env recognition than monkeys immunized with vaccines including a single Env immunogen. All groups of vaccinated monkeys demonstrated equivalent immune protection following challenge with the pathogenic simian-human immunodeficiency virus 89.6P. These data suggest that a multicomponent vaccine encoding Env proteins from multiple clades of HIV-1 can generate broad Env-specific T-lymphocyte and antibody responses without antigenic interference. This study demonstrates that it is possible to generate protective immune responses by vaccination with genetically diverse isolates of HIV-1.


2001 ◽  
Vol 75 (9) ◽  
pp. 4430-4434 ◽  
Author(s):  
James P. McGettigan ◽  
Heather D. Foley ◽  
Igor M. Belyakov ◽  
Jay A. Berzofsky ◽  
Roger J. Pomerantz ◽  
...  

ABSTRACT Novel viral vectors that are able to induce both strong and long-lasting immune responses may be required as effective vaccines for human immunodeficiency virus type 1 (HIV-1) infection. Our previous experiments with a replication-competent vaccine strain-based rabies virus (RV) expressing HIV-1 envelope protein from a laboratory-adapted HIV-1 strain (NL4–3) and a primary HIV-1 isolate (89.6) showed that RV-based vectors are excellent for B-cell priming. Here we report that cytotoxic T-lymphocyte (CTL) responses against HIV-1 gp160 are induced by recombinant RVs. Our results indicated that a single inoculation of mice with an RV expressing HIV-1 gp160 induced a solid and long-lasting memory CTL response specific for HIV-1 envelope protein. Moreover, CTLs from immunized mice were not restricted to the homologous HIV-1 envelope protein and were able to cross-kill target cells expressing HIV-1 gp160 from heterologous HIV-1 strains. These studies further suggest promise for RV-based vectors to elicit a persistent immune response against HIV-1 and their potential utility as efficacious anti-HIV-1 vaccines.


2005 ◽  
Vol 79 (18) ◽  
pp. 12100-12105 ◽  
Author(s):  
Thillagavathie Pillay ◽  
Hua-Tang Zhang ◽  
Jan W. Drijfhout ◽  
Nicola Robinson ◽  
Helen Brown ◽  
...  

ABSTRACT The role of cytotoxic T-lymphocyte (CTL) escape in rapidly progressive infant human immunodeficiency virus type 1 (HIV-1) infection is undefined. The data presented here demonstrate that infant HIV-1-specific CTL can select for viral escape variants very early in life. These variants, furthermore, may be selected specifically in the infant, despite the same CTL specificity being present in the mother. Additionally, pediatric CTL activity may be compromised both by the transmission of maternal escape variants and by mother-to-child transmission of escape variants that originally arose in the father. The unique acquisition of these CTL escape forms may help to explain the severe nature of some pediatric HIV infections.


1999 ◽  
Vol 73 (8) ◽  
pp. 6715-6720 ◽  
Author(s):  
Spyros A. Kalams ◽  
S. P. Buchbinder ◽  
E. S. Rosenberg ◽  
J. M. Billingsley ◽  
D. S. Colbert ◽  
...  

ABSTRACT Cellular immune responses are thought to be an important antiviral host defense, but the relationship between virus-specific T-helper and cytotoxic-T-lymphocyte (CTL) responses has not been defined. To investigate a potential link between these responses, we examined functional human immunodeficiency virus type 1 (HIV-1)-specific memory CTL precursor frequencies and p24-specific proliferative responses in a cohort of infected untreated persons with a wide range of viral loads and CD4 cell counts. Levels of p24-specific proliferative responses positively correlated with levels of Gag-specific CTL precursors and negatively correlated with levels of plasma HIV-1 RNA. These data linking the levels of HIV-specific CTL with virus-specific helper cell function during chronic viral infection provide cellular immunologic parameters to guide therapeutic and prophylactic vaccine development.


2005 ◽  
Vol 79 (14) ◽  
pp. 9363-9366 ◽  
Author(s):  
Charles T. T. Edwards ◽  
Katja J. Pfafferott ◽  
Philip J. R. Goulder ◽  
Rodney E. Phillips ◽  
Edward C. Holmes

ABSTRACT The hypothesis that the intrapatient emergence of cytotoxic T-lymphocyte escape variants contributes to the evolution of human immunodeficiency virus type 1 at the population (interpatient) level was tested using the HLA-A*0201-restricted gag p17 epitope SLYNTVATL. Using a simple experimental design, we investigated the evolutionary processes operating within this epitope among patients while compensating for the confounding influence of intrapatient natural selection. Using this approach, we revealed a pattern of A*0201-driven escape within patients, followed by the sustained transmission of these escape variants among patients irrespective of their HLA type.


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