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Antibody Recognition of the Dengue Virus Proteome and Implications for Development of Vaccines
NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
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Dengue is a mosquito-borne infection caused by four distinct serotypes of dengue virus, each appearing cyclically in the tropics and subtropics along the equator. Although vaccines are currently under development, none are available to the general population. One of the main impediments to the successful advancement of these vaccines is the lack of well-defined immune correlates of protection. Here, we describe a protein microarray approach for measuring antibody responses to the complete viral proteome comprised of the structural capsid, membrane, and envelope and nonstructural NSl, NS2A, NS28, NS3, NS4A, NS48, and NSS components of all four dengue virus serotypes 1 to 4. We examined rhesus macaques vaccinated with tetravalent vaccines consisting of live-attenuated virus LA V or purified inactivated virus PIV, followed by boosting with LA V and challenging with wild-type dengue virus. We detected temporal increases in antibodies against envelope proteins in response to either vaccine, while only the PIVLA V vaccination strategy resulted in anticapsid antibodies. In contrast to results from vaccination, naive macaques challenged with wild-type viruses of each serotype demonstrated a balanced response to nonstructural and structural components, including responses against the membrane protein. Our results demonstrate discriminating details concerning the nature of antibody responses to dengue virus at the proteomic level and suggest the usefulness of this information for vaccine development.
APPROVED FOR PUBLIC RELEASE