Showing papers on "SAIDS Vaccines published in 2014"
Vaccine Research Center1, Science Applications International Corporation2, George Washington University3, Los Alamos National Laboratory4, Duke University5, Sanofi Pasteur6, Harvard University7, Beth Israel Deaconess Medical Center8, Fred Hutchinson Cancer Research Center9, National Institutes of Health10
TL;DR: A nonhuman primate challenge model with simian immunodeficiency virus (SIV) shows that antibodies to the SIV envelope are necessary and sufficient to prevent infection, and identifies a two-amino-acid signature that alters antigenicity and confers neutralization resistance.
Abstract: A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV) We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies These analyses provide insight into the limited efficacy seen in HIV vaccine trials The analysis of multiple SIV vaccine regimens in macaques leads to the identification of a key two-amino-acid signature that confers resistance to neutralizing antibodies; a similar mechanism of immune escape is shown to operate in HIV and may explain the limited efficacy seen in HIV vaccine trials Clinical trials of human immunodeficiency virus-1 (HIV-1) vaccines have so far proved disappointing, achieving either low-level efficacy or zero protection Here Mario Roederer et al analyse the effects of multiple vaccine regimens in the macaque simian immunodeficiency virus (SIV) model and identify a key two-amino-acid signature that confers resistance to neutralizing antibodies A similar mechanism of immune escape is shown to operate in HIV, suggesting that this type of vaccine-elicited antibody response may explain the limited efficacy seen in HIV vaccine trials
142 citations
TL;DR: Findings obtained with the simian immunodeficiency virus (SIV) monkey model have provided new evidence that stimulating effective CD8+ T cell immunity could provide protection, and in this Perspective the path forward for optimizing such responses in humans is explored.
Abstract: The search for a vaccine against human immunodeficiency virus type 1 (HIV-1) has many hurdles to overcome. Ideally, the stimulation of both broadly neutralizing antibodies and cell-mediated immune responses remains the best option, but no candidate in clinical trials at present has elicited such antibodies, and efficacy trials have not demonstrated any benefit for vaccines designed to stimulate immune responses of CD8(+) T cells. Findings obtained with the simian immunodeficiency virus (SIV) monkey model have provided new evidence that stimulating effective CD8(+) T cell immunity could provide protection, and in this Perspective we explore the path forward for optimizing such responses in humans.
79 citations
TL;DR: It is demonstrated that BCG-SIVgag is able to elicit robust transgene-specific priming responses, resulting in strong SIV epitope-specific cellular immune responses, suggesting that combining this approach with other immunogens may contribute to the development of effective vaccine regimens against HIV.
Abstract: Live attenuated nonpathogenic Mycobacterium bovis bacillus Calmette-Guerin (BCG) mediates long-lasting immune responses, has been safely administered as a tuberculosis vaccine to billions of humans, and is affordable to produce as a vaccine vector. These characteristics make it very attractive as a human immunodeficiency virus (HIV) vaccine vector candidate. Here, we assessed the immunogenicity of recombinant BCG (rBCG) constructs with different simian immunodeficiency virus (SIV)gag expression cassettes as priming agents followed by a recombinant replication-incompetent New York vaccinia virus (NYVAC) boost in rhesus macaques. Unmutated rBCG constructs were used in comparison to mutants with gene deletions identified in an in vitro screen for augmented immunogenicity. We demonstrated that BCG-SIVgag is able to elicit robust transgene-specific priming responses, resulting in strong SIV epitope-specific cellular immune responses. While enhanced immunogenicity was sustained at moderate levels for >1 year following the heterologous boost vaccination, we were unable to demonstrate a protective effect after repeated rectal mucosal challenges with pathogenic SIVmac251. Our findings highlight the potential for rBCG vaccines to stimulate effective cross-priming and enhanced major histocompatibility complex class I presentation, suggesting that combining this approach with other immunogens may contribute to the development of effective vaccine regimens against HIV.
13 citations