Antibody Recognition of the Dengue Virus Proteome and Implications for Development of Vaccines
Abstract
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 PIV/LA 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2011
- Accession Number
- ADA552121
Entities
People
- Alexander P. Tikhonov
- Barry Schweitzer
- Emily D. Cisney
- Monika Simmons
- Robert G Ulrich
- Robert J. Putnak
- Stefan Fernandez
Organizations
- Naval Medical Research Center