Article

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: 4.65). 04/2005; 79(5):2956-63. DOI: 10.1128/JVI.79.5.2956-2963.2005
Source: PubMed

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.

0 Followers
 · 
61 Views
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Vaccines are arguably the most powerful medical intervention in the fight against infectious diseases. The enormity of the global human immunodeficiency virus type 1 (HIV)/acquired immunodeficiency syndrome (AIDS) pandemic makes the development of an AIDS vaccine a scientific and humanitarian priority. Research on vaccines that induce T-cell immunity has dominated much of the recent development effort, mostly because of disappointing efforts to induce neutralizing antibodies through vaccination. Whereas T cells are known to limit HIV and other virus infections after infection, their role in protection against initial infection is much less clear. In this article, we will review the rationale behind a T-cell-based vaccine approach, provide an overview of the methods and platforms that are being applied, and discuss the impact of recent vaccine trial results on the future direction of T-cell vaccine research.
    Cold Spring Harbor Perspectives in Medicine 09/2011; 1(1):a007252. DOI:10.1101/cshperspect.a007252 · 7.56 Impact Factor
  • Source
    • "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 . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mycobacterium bovis bacille Calmette-Guérin (BCG) is the only available vaccine for tuberculosis (TB). Although this vaccine is effective in controlling infantile TB, BCG-induced protective effects against pulmonary diseases in adults have not been clearly demonstrated. Recombinant BCG (rBCG) technology has been extensively applied to obtain more potent immunogenicity of this vaccine, and several candidate TB vaccines have currently reached human clinical trials. On the other hand, recent progress in the improvement of the BCG vector, such as the codon optimization strategy and combination with viral vector boost, allows us to utilize this bacterium in HIV vaccine development. In this paper, we review recent progress in rBCG-based vaccine studies that may have implications in the development of novel vaccines for controlling global infectious diseases in the near future.
    05/2011; 2011:574591. DOI:10.1155/2011/574591
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate essential factors that determine the efficacy of vaccines against lentiviruses, an effective attenuated equine infectious anemia virus (EIAV) vaccine strain and a proviral derivative of the vaccine were compared with respect to differences in inducing protective immunity. Although these two strains replicated equally well in vitro and in vivo, the proviral strain induced significantly less protection from disease and infection caused by viral challenge and significantly lower specific neutralizing capability. These findings indicated that the proviral strain had lost the ability to stimulate immune protection compared to the parental vaccine strain. A further analysis of the envelope gp90 gene variation revealed that compared to the proviral strain, the vaccine strain displayed a wide sequence diversity in immunogen composition. Thus, we inferred that the differences in immunogen composition might be the major cause for the failure of the proviral derivative to elicit the immune protection induced by the parental strain.
    Virology 02/2011; 410(1):96-106. DOI:10.1016/j.virol.2010.10.032 · 3.28 Impact Factor

Preview

Download
0 Downloads
Available from