Sunday, September 11, 2016

If Tirumalai Kamala could have one source of funding, would it be from a major government (US, Canada, Europe, etc.) or from private enterprise?


I'd choose private enterprise any day. For several reasons. By now, it's rather clear government funding of research is stuck in a rut. Highly risk-averse. Grant reviewers part of a well-ensconced old boys club with no signs of impending unseating. Younger generation being trained in the same mould. Result? Same old, same old. I'll illustrate with one telling example. HIV. Appeared on the radar in the early 1980s. 1984 is when Anthony S. Fauci became Director of NIAID (National Institute of Allergy and Infectious Diseases), the US government's premier research agency tasked with infectious disease research. 32 years and counting at the helm, no sign of an approved prophylactic or even a therapeutic HIV vaccine. This wasn’t because enough resources weren’t committed to the task. During the height of NIH's gravy train from 1998 to 2003 when its budget doubled, a sizeable chunk unsurprisingly made its way into NIAID which set about creating its own vaccine research wing, the Vaccine Research Center. Established with much fanfare in 1999, still no approved HIV vaccine on the horizon.  

Meantime, in 2014 a privately funded French group published a highly novel mode of vaccine protection against SIV, the monkey version of HIV (1). Using a highly unorthodox vaccination, either in the stomach or the vagina, all three vaccines they tried protected against SIV. The protection mechanism was completely unexpected and novel. Not antibodies. Not cytotoxic killer cells. Rather a new type of regulatory CD8 T cell that suppressed the activation of SIV-specific CD4 T cells. Why is that so important? SIV/HIV activate CD4 T cells, apparently for their own purpose. Activated CD4 T cells are the Trojan horses SIV/HIV use to establish stable infection in the body. Trojan horse because activated CD4 T cells also proliferate actively. Situation tailor-made for creating more cells for SIV/HIV to infect. By halting such CD4 T cell activation, these unconventional CD8 T cells are stopping SIV in its tracks. Maybe same could happen with HIV as well.
The same group published preliminary data from this series of studies in 2012 (2), data that sank like a stone in the tight-knit HIV research community. As Jose Esparza and Marc HV Van Regenmortel editorialize (3),
“The 2012 publication from this group had very little impact in the field, perhaps because it was received with a degree of skepticism. After all, 30 years of intense vaccine research had not resulted in a practical effective vaccine, although an HIV vaccine is sorely needed to bring the HIV epidemic under control. No stone should remain unturned in its search, and the approach reported in this journal should not be dismissed a priori. Instead, it should be carefully considered by other scientists and appropriately confirmed or refuted by additional research”. “Out-of-the- paradigm approaches, such as the one proposed by Andrieu et al., should be further explored”.
And Marc HV Van Regenmortel further elaborated about their earlier 2012 study (4)
“This remarkable and totally unexpected breakthrough was obtained by an investigator-driven research that was not funded by the usual governmental and large scale organizations that support most of the ongoing HIV vaccine research world-wide. It was sponsored by a private benefactor who funded the project to the tune of 13 million Euros. This illustrates once again that success in basic vaccine research is unpredictable and that “risky” projects based on unorthodox thinking may deserve as much funding as the “safe” projects that are often preferred because they abide by current fashionable paradigms”.
Bibliography
1. Andrieu, Jean-Marie, et al. "Mucosal SIV vaccines comprising inactivated virus particles and bacterial adjuvants induce CD8+ T-regulatory cells that suppress SIV-positive CD4+ T-cell activation and prevent SIV infection in the macaque model." Frontiers in immunology 5 (2014). http://www.ncbi.nlm.nih.gov/pmc/... 
2. Lu, Wei, et al. "Induction of CD8+ regulatory T cells protects macaques against SIV challenge." Cell reports 2.6 (2012): 1736-1746. http://www.sciencedirect.com/sci...
3. Esparza, José, and Marc HV Van Regenmortel. "More surprises in the development of an HIV vaccine." Frontiers in immunology 5 (2014): 329. http://www.ncbi.nlm.nih.gov/pmc/... 
4. Regenmortel, M. H. V. V. "An oral tolerogenic vaccine protects macaques from SIV infection without eliciting SIV-specific antibodies nor CTLs." J AIDS Clin Res 4 (2013): e112. http://www.omicsonline.org/2155-...



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