HIV vaccine setback - September 24, 2007
HIV researchers suffered a blow at the weekend when drug company Merck pulled a major vaccine trial (BBC, AFP, AP, NY Times, press release). Testing of the V520 vaccine was stopped after it was found to be ineffective. “It is a huge disappointment because this vaccine has shown promise all the way through, but it's only when you get in on these big trials that you start to see how the vaccine behaves. Although in earlier studies we saw beautiful immune responses, it doesn't look like this immune response translates into something that could protect people against HIV infection,” said Glenda Gray, one of the principal investigators (AFP).
The vaccine used a weakened version of a common cold virus carrying three synthetic HIV genes. The trial enrolled 3,000 HIV-negative volunteers at high risk of HIV infection at sites around the world. An interim analysis conducted on half of these people found no benefit from the vaccine. There were 24 cases of infection in the 741 participants who received the vaccine and 21 cases in the 762 who didn’t.
Image: HIV virus / Getty
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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
www.oloscience.com
Posted by: Fausto Intilla | October 17, 2007 07:55 PM
Intense persuasion, over expression of PPAR will initiate the adaptive immune system. A chronic immune response maybe interpreted as weak metabolic signaling. The involved dendritic cells, T cells and macrophages have not been provoked beyond tolerance. Using nicotinic acid to over express PPAR will cause unfurling of complement genes. Complete genes expression will improve dendrite cells to form MHC, T cells to increase TNF and macrophage phagocytotis. Improved functions of PPAR will also facilitate the ubiquitin-proteasome system, and other pathways. The enhanced metabolic signals will provoke the adaptive immune system to differentiate lymphocytes to memory T cells and memory B cells. Any chronic infection that has establishes suboptimal activation of dendritic cells, memory B cells and of macrophages can be eradicated once metabolic signals are enhanced.
Achieving full immunity will occur between six to nine months. The ability of pathogens to use camouflage, such as ceramide, will not shield it. The efficacy of nicotinic acid can be impaired by agents (including lysine) that suppress transcription activities. Viral infected subjects must be healthy to endure the six to nine months. Those subjects with genital herpes should expect an outbreak each 28-days cycle for six months. Aspirin may help to limit the pro-inflammatory response. Subjects with drug resistant bacterial infection will be able to continue antibiotic therapy. The timescale for adaptive immunity is typical of a vaccine regiment.
Nicotinic acid (flush-free or slow release) dosage is 1500 to 2000mg, divided doses, per day for six months. The dose is lowered to 1000 to 1500mg, divided doses, per day for the next six to twelve months.
Posted by: Norman A. Smith | March 13, 2008 05:27 PM