Another HIV Vaccine Trial Bust
Tuesday, September 25th 2007
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Apparently In Vivo The Stimulation of CTLs by the Vaccine Didn’t Decrease The Risk of Infection
Disappointment as Merck’s live recombinant vaccine fails in its Phase III trial,
Executives at the company, based in Whitehouse Station, N.J., said 24 of 741 volunteers who got the vaccine in one segment of the experiment later became infected with HIV, the virus that causes AIDS. In a comparison group of volunteers who got dummy shots, 21 of 762 participants became infected.
More on Merck’s HIV vaccine efforts here and more on HIV vaccine efforts in general at the WHO.
Source: http://www.sciencedaily.com/releases/2007/10/071012080135.htm
Science Daily — The search for a vaccination against HIV has been in progress since 1984, with very little success. Traditional methods used for identifying potential cellular targets can be very costly and time-consuming.
The key to creating a vaccination lies in knowing which parts of the pathogen to target with which antibodies. A new study by David Heckerman and colleagues from Massachusetts General Hospital, publishing in PLoS Computational Biology, has come up with a way to match pathogens to their antibodies.
At the core of the human immune response is the train-to-kill mechanism in which specialized immune cells are sensitized to recognize small peptides from foreign pathogens (e.g., HIV). Following this sensitization, these cells are then activated to kill cells that display this same peptide. However, for sensitization and killing to occur, the pathogen peptide must be “paired up” with one of the infected person’s other specialized immune molecules–an HLA (human leukocyte antigen) molecule. The way in which pathogen peptides interact with these HLA molecules defines if and how an immune response will be generated.
Heckerman’s model uses ELISpot assays to identify HLA-restricted epitopes, and which HLA alleles are responsible for which reactions towards which pathogens. The data generated about the immune response to pathogens fills in missing information from previous studies, and can be used to solve a variety of similar problems.
The model was applied to data from donors with HIV, and made 12 correct predictions out of 16. This study, says David Heckerman, has “significant implications for the understanding of…vaccine development.” The statistical approach is unusual in the study of HLA molecules, and could lead the way to developing an HIV vaccine.
Citation: Listgarten J, Frahm N, Kadie C, Brander C, Heckerman D (2007) A statistical framework for modeling HLA-dependent T cell response data. PLoS Comput Biol 3(10): e188. doi:10.1371/journal.pcbi.0030188
Note: This story has been adapted from material provided by Public Library of Science.
Fausto Intilla
http://www.oloscience.com