Multiclade Human Immunodeficiency Virus Type 1 Envelope Immunogens Elicit Broad Cellular and Humoral Immunity in Rhesus Monkeys

Beth Israel Deaconess Medical Center, Division of Viral Pathogenesis, 330 Brookline Ave./RE-113, Boston, MA 02215, USA.
Journal of Virology (Impact Factor: 4.44). 04/2005; 79(5):2956-63. DOI: 10.1128/JVI.79.5.2956-2963.2005
Source: PubMed


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.

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    • "This approach is also being applied to HIV in which vaccines based on three or more strains of HIV are being tested. This approach clearly increases the likelihood that the T-cell response will recognize more than one strain of HIV (Seaman et al. 2005), however, the cost and complexity of a vaccine increases significantly with each new strain that is added, and it is difficult to determine the impact of vaccine valency in actual protection in human clinical trials. HIV sequence alignments and knowledge of where T-cell epitopes reside within those alignments have been used to generate HIV antigens that encompass the most prevalent HIV strain sequences within just one or a few constructs. "
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    • "Based on these findings, various vaccine modalities, including live viral vectors and DNA vaccines, have been used to elicit strong CTL and Th1 type Tuberculosis Research and Treatment responses in nonhuman primate models. Although singlevaccine delivery systems sometimes exhibit insufficient immune responses, boosting with viral vector vaccines such as vaccinia virus [40] [41], adenovirus [42] [43], and Sendai virus [44] in DNA-primed individuals strongly amplified CTL responses and resulted in the effective control of simian immunodeficiency virus (SIV) replication. Among such viral vectors, adenovirus type 5 (Ad5) had the strongest CTL enhancement effect, and the DNA-prime and recombinant Ad5 boost vaccine strategy is recognized as the most promising . "
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    • "This vaccine strategy involves the generation of immunogen diversity by utilizing differential envelope proteins from different strains. Preclinical and clinical experiments have suggested that this type of vaccine has potential advantages in the induction of immune responses over immunogens with a single envelope protein, especially because the combinatorial use of diverse immunogens can result in an expanded spectrum of neutralizing antibodies that are induced by these vaccines (Cho et al., 2001; Hurwitz et al., 2005; Sealy et al., 2009; Seaman et al., 2005). The results of the present study revealed that the average difference in the gp90 amino acid sequences was 3% among the major quasispecies in the attenuated vaccine strain. "
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