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The Washington Research Foundation Fellowship
Sergei Ivanov, Microbiology - 2008-09 WRFF
Upon entering the University of Washington my main interests focused on science and discovering, as well as participating in, the mechanisms by which it provided for the welfare of the world. In short, I liked thinking and learning about science, but truly had no idea of what actually was incorporated in the idea of it. I didn’t have to wait long, however, in my first quarter at UW my views and interests would be drastically influenced. I took an anthropology class as a part of the UW Honors Freshman Interest Group and discovered a world of science that would motivate me to initiate my journey of wanting to make a difference. This class focused on a study of the Igbo Tribe of South East Nigeria. We dove into the abstract and mystic mechanisms by which their culture operates, and by the end of the quarter I had managed to bridge the ideas of this anthropological study with my passion for science, revealing to myself a drastically underrepresented field of research that bridged the boundary between the study of infectious disease and culture, producing a mechanism by which a sustainable idea of Public Health can be achieved. Since then, I have continued on this path by participating in research, studying HIV-1 in low-level infected patients that span the globe and serve as the most promising human model to limit HIV-1 infection to such low levels that they no longer bring about immunodeficiency. This research is the first learning experience on my path of success. It serves as a key ingredient that allows me to achieve an in depth understanding of this issue from the perspective of microbiology, which is no doubt essential in working for a cure to some of the world’s greatest health disasters. I have also conducted an ethnographic research study in Sierra Leone during the summer of my freshman year, which is still on going. I’m very thankful to the WRFF for their grant enabling me to continue this research and the pursuit of goals.
Mentor: Tuofu Zhu, Laboratory Medicine
Project Title: Genetic Analysis of HIV-1 in Individuals with Extraordinarily Low Level HIV-1 Infections (ELLHI) in Global Populations
Abstract: Vaccines are the most effective and affordable public health interventions to halt the HIV pandemic. Unfortunately, a preventive vaccine is not a realistic immediate goal. Instead, vaccine efforts are currently focused on a hypothesis that has shown promise in SIV-monkey models – namely a vaccine that will keep the virus in check to such low levels that the likelihood of transmission and disease progression will be significantly reduced. However, fundamental differences between SIV and HIV-1 preclude direct extrapolation of vaccine correlates from monkey models to human infection. The need for pioneering new approaches to AIDS vaccine design became even more apparent after Merck's leading candidate, MRKAd5, which showed promising control of virus levels post-infection in monkeys, failed to provide any degree of protection against or control of HIV-1 infection in humans. Thus, understanding how to protect against HIV ultimately requires evaluation of its natural host - humans.
There is general consensus that studying individuals who are repeatedly exposed to HIV-1 yet remain uninfected may provide invaluable information to aid in the design of vaccines and therapeutic approaches. An important issue is to determine whether a proportion of these “HIV-protected” persons harbor low levels of HIV-1 infection. Unfortunately, almost all cases of such extraordinarily low level HIV-1 infections (ELLHI) reported by conventional technologies appear to be due to laboratory error, or are without sufficient confirmatory studies. This is primarily due to the lack of methodologies that are sensitive and specific enough to convincingly detect ELLHI.
The Zhu Lab has shown, for the first time, that people who can control HIV-1 at extremely low levels exist in Seattle, which represents the most relevant human model of HIV-1 control for vaccine development. Such ELLHIs have been proven by developing and employing a sensitive and laborious nested PCR assay. Most recently, The Zhu Lab has improved upon the technology of this ultrasensitive assay by markedly increasing the throughput. This allows for more population-based research, examining the frequency of such ELLHI in high-risk communities that are afflicted by HIV-1 in diverse regions of the world.