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Clin. Vaccine Immunol. doi:10.1128/CVI.00045-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Dose-dependent protection or exacerbation of disease by a PLG microparticle-adsorbed, alphavirus-based measles DNA vaccine in rhesus macaques

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA; Departments of Molecular and Comparative Pathobiology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA; and Chiron Corporation, Emeryville, California 94608, USA

^* To whom correspondence should be addressed. Email: dgriffin{at}jhsph.edu.

	Abstract

Measles remains an important cause of vaccine-preventable child mortality. Development of a low-cost, heat-stable vaccine for infants under the age of 6 months could improve measles control by facilitating delivery at the time of other vaccines and by closing a window of susceptibility prior to immunization at 9 months of age. DNA vaccines hold promise for development, but achieving protective levels of antibody has been difficult and there is an incomplete understanding of protective immunity. In the current study, we evaluated the use of a layered alphavirus DNA/RNA vector encoding measles virus H (SINCP-H) adsorbed onto polylactide glycolide (PLG) microparticles. In mice, antibody and T cell responses to PLG-formulated DNA were substantially improved compared to naked DNA. Rhesus macaques received two doses of PLG/SINCP-H delivered either intramuscularly (0.5mg) or intradermally (0.5 or 0.1 mg). Antibody and T cell responses were induced, but not sustained. On challenge, the intramuscularly vaccinated monkeys did not develop rashes and had lower viremias than vector control monkeys. Monkeys vaccinated with the same dose intradermally developed rashes and viremia. The low dose intradermally vaccinated monkeys developed more severe rashes, with histopathologic evidence of syncytia and intense dermal and epidermal inflammation, eosinophilia and higher viremia compared to vector control monkeys. Protection after challenge correlated with IFN--producing T cells and with early production of high avidity antibody that bound wild type H protein. We conclude that PLG/SINCP-H is most efficacious when delivered intramuscularly, but does not provide an advantage over standard DNA vaccines for protection against measles.

This article has been cited by other articles:

• Pan, C.-H., Jimenez, G. S., Nair, N., Wei, Q., Adams, R. J., Polack, F. P., Rolland, A., Vilalta, A., Griffin, D. E. (2008). Use of Vaxfectin Adjuvant with DNA Vaccine Encoding the Measles Virus Hemagglutinin and Fusion Proteins Protects Juvenile and Infant Rhesus Macaques against Measles Virus. CVI 15: 1214-1221 [Abstract] [Full Text]