This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pan, C.-H.
Right arrow Articles by Griffin, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pan, C.-H.
Right arrow Articles by Griffin, D. E.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, April 2008, p. 697-706, Vol. 15, No. 4
1071-412X/08/$08.00+0     doi:10.1128/CVI.00045-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Dose-Dependent Protection against or Exacerbation of Disease by a Polylactide Glycolide Microparticle-Adsorbed, Alphavirus-Based Measles Virus DNA Vaccine in Rhesus Macaques{triangledown}

Chien-Hsiung Pan,1 Nitya Nair,1 Robert J. Adams,2 M. Christine Zink,1,2 Eun-Young Lee,1 Fernando P. Polack,1,3 Manmohan Singh,4 Derek T. O'Hagan,4 and Diane E. Griffin1*

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205,1 Departments of Molecular and Comparative Pathobiology,2 Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21218,3 Novartis Vaccines, Emeryville, California 946084

Received 5 February 2008/ Accepted 7 February 2008

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 those to naked DNA. Rhesus macaques received two doses of PLG/SINCP-H delivered either intramuscularly (0.5 mg) 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-treated control monkeys. Monkeys vaccinated with the same dose intradermally developed rashes and viremia. Monkeys vaccinated intradermally with the low dose developed more severe rashes, with histopathologic evidence of syncytia and intense dermal and epidermal inflammation, eosinophilia, and higher viremia compared to vector-treated control monkeys. Protection after challenge correlated with gamma interferon-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.

* Corresponding author. Mailing address: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205. Phone: (410) 955-3459. Fax: (410) 955-0105. E-mail: dgriffin{at}jhsph.edu

{triangledown} Published ahead of print on 20 February 2008.

Clinical and Vaccine Immunology, April 2008, p. 697-706, Vol. 15, No. 4
1071-412X/08/$08.00+0     doi:10.1128/CVI.00045-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»