Research Project: It is crucial that a global strategy be formulated to safely phase out polio vaccination after wild type polio eradication. The Sabin oral polio vaccine (OPV), currently used in most of the developing world, is inexpensive and effective. However, as a live virus, it has the capacity to spread and mutate into neurovirulent forms capable of causing outbreaks. If all polio vaccination is stopped abruptly, there would be a real threat of the OPV still in circulation causing outbreaks of paralytic poliomyelitis among the youngest, unvaccinated children. The safest strategy after wild poliovirus eradication would be to globally stop using all OPV and use inactivated polio vaccine (IPV) until all OPV is out of circulation. IPV is much more expensive than OPV and produces inferior intestinal immunity, but it prevents paralytic poliomyelitis and cannot mutate into neurovirulent forms. However, there is little data on how long OPV would continue to circulate in a community after it switches to IPV use. This study aims to fill this knowledge gap. Mexico switched from OPV to IPV as part of its primary vaccination regimen in 2007, but it still conducts semiannual national immunization days (NIDs) in which OPV is given. I plan to conduct a longitudinal study in Orizaba, Mexico, collecting stool and sewage samples monthly over one year to determine exactly how long OPV stays in circulation, to establish if the duration of circulation differs between urban and rural populations, and to determine the frequency and rate at which OPV develops into mutant strains. My hypothesis is that OPV will stop circulating in a community in which infants are routinely immunized with IPV by 6 months after an NID. Candidate: My overall goal is to become a successful academic physician scientist in the field of translational research with an initial focus on OPV circulation and immunogenicity and a longer term goal of conducting research on vaccine-preventable infections that most affect the developing world. The K23 Career Development Award (CDA) would provide me with the additional training and mentoring necessary to establish an independent, patient-oriented research career. I have sought out opportunities to conduct research, teach, and solidify my clinical skills throughout my training. In the last two years, I have learned how to design and manage international studies and perform and validate state-of-the-art laboratory assays to detect and characterize OPV and its mutant forms in clinical samples. I designed and successfully completed the pilot study in Mexico on which the longitudinal study described in this CDA is based. I would use the protected time provided by the CDA to complete the longitudinal study under the mentorship of my training committee, while expanding my knowledge of biostatistics and epidemiology, immunology, laboratory techniques, and Spanish through coursework and practical training. Environment: Stanford has copious resources to facilitate the successful completion of this project and my development into an independent researcher. I will perform this research under the primary mentorship of Dr. Yvonne Maldonado, an expert on OPV shedding and mutation and a veteran of numerous collaborative international studies. Her laboratory has the necessary space and equipment to analyze samples for OPV and its mutant forms, and she has statisticians on staff to provide guidance with the data analysis. My training committee is also comprised of two co-mentors and two consultants who between them have decades of experience in international patient-oriented research, vaccine studies in Mexico, and laboratory analysis of OPV. Stanford also has a wealth of opportunities for advanced coursework and training through the main university, the medical school, and the Stanford Center for Clinical and Translational Education and Research. Relevance: This application aims to study how long oral polio vaccine circulates in a Mexican community primarily protected by the inactivated polio vaccine. Oral polio vaccine is used in most developing countries to prevent poliomyelitis, but it can also cause outbreaks of paralytic poliomyelitis when it acquires certain mutations through prolonged circulation in undervaccinated communities. Our findings would help world policy makers devise the best and safest strategy to globally phase out polio vaccination after wild poliovirus eradication.
This application aims to study how long oral polio vaccine circulates in a Mexican community primarily protected by the inactivated polio vaccine. Oral polio vaccine is used in most developing countries to prevent poliomyelitis, but it can also cause outbreaks of paralytic poliomyelitis when it acquires certain mutations through prolonged circulation in undervaccinated communities. Our findings would help world policy makers devise the best and safest strategy to globally phase out polio vaccination after wild poliovirus eradication.
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