Towards a Vaccine for HIV: Cytokines

RAUL JORDAN

b cytokineWhile long-standing attempts at developing a vaccine for HIV have met with little success, newer experiments have explored ways to help people achieve immunity through proteins. My research focuses on molecules called cytokines, proteins that regulate hormones and help cells communicate with each other. By stimulating cytokine receptors to produce HIV-fighting proteins like transforming growth factor (TGF), high concentrations of one particular cytokine, IL-16, can actually cause a significant decrease in HIV virus (Amiel, Corinne, & Darcissac, 1999).

Under the mentorship of immunologist Dr. Jose Villareal at the Centro de Salud in San Pedro, Honduras, I used protein imaging software to map out the structure of IL-16 and analyze exactly how it acts on other cytokine receptors. I found that the protein could stimulate the production of the other cytokines, but that could also affect the production of the protein, due to the characteristic helix bundle shape of IL-16. This might hold implications for the hopes of immunology against HIV/AIDS. By stimulating the conformational shape of IL-16 through an engineered “vaccine”, it could be possible for an individual to develop immunity to HIV-1 by cell-mediated cytokine interaction patterns that involve large concentrations of this IL-16.

[…] my ongoing research has focused on molecules called cytokines, which are a group of proteinaceous signaling substances that have effects on various cells in the body.

Part of my research also involved taking periodic samples of the plasma serum of a set of HIV positive individuals’ blood and determining whether white blood cell counts would rise if they had higher IL-16 levels in their immune system. Indeed, an overall high concentration of IL-16 helped stabilize the amount of white blood cells. Individuals with higher concentrations of IL-16 had white blood cell counts that did not decrease as quickly as in individuals with lower IL-16 concentrations. However, this was a result of a coordinated effort of many cytokines, and this strategy to tackle HIV would only work if all these interactions are IL-16 mediated. One of the greatest breakthroughs for this phenomenon would be to determine the exact location and time of the production of these cytokines in order to comprehend the mechanism better.

I am currently developing possible methods of implementing the stimulated production of IL-16 in the immune system. By using PYMOL and studying biophysical interactions such as the progression and rates of occurrence behind the different cytokine signaling pathways, I hope to obtain a better understanding of their coordinated behavior in fighting the HIV-1 virus. While many comparative studies have been made on rhesus monkeys infected with the Simian Immunodeficiency Virus and their reaction to cytokine-mediated immunity (Lairmore, Post, Goldsmith, & Folks, 1991), there are not as many analyses of the quantitative biophysics behind this interaction in humans. As new technologies emerge, immunity to HIV-1 could emerge as more than a simply theoretical and far-fetched idea—it might someday become a tangible phenomenon that will change the world in ways previously unimaginable.

References:

1.   Amiel, C., Darcissac, E., Truong, M., Dewulf, J., Loyens, M., Mouton, Y., et al. (1999). Interleukin‐16 (IL‐16) Inhibits Human Immunodeficiency Virus Replication In Cells From Infected Subjects, And Serum IL‐16 Levels Drop With Disease Progression. The Journal of Infectious Diseases179(1), 83-91.

2.   Knox, R. (2013, April 26). Failure Of Latest HIV Vaccine Test: A ‘Huge Disappointment’. NPR. Retrieved November 25, 2013, from http://www.npr.org/blogs/health/2013/04/26/179231916/failure-of-latest-hiv-vaccine-test-a-huge-disappointment

3.   Lairmore, M., Post, A., Goldsmith, C., & Folks, T. (1991). Cytokine Enhancement of Simian Immunodeficiency Virus (SIV/mac) from a Chronically Infected Cloned T-cell Line (HuT-78). Archives of Virology121(1-4), 43-53.

4.   Uchil, P., Hinz, A., & Siegel, S. (2013). TRIM Protein-Mediated Regulation of Inflammatory and Innate Immune Signaling and Its Association with Antiretroviral Activity. American Society for Microbiology87(2). Retrieved June 3, 2013, from jvi.asm.org

Raul Jordan is a Brevia staff writer. He can be reached at rauljordan@college.harvard.edu.
Featured image credit: New York Academy of Sciences