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
Services
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 Dunachie, S. J.
Right arrow Articles by Hill, A. V. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dunachie, S. J.
Right arrow Articles by Hill, A. V. S.

 Previous Article  |  Next Article 

Infection and Immunity, October 2006, p. 5933-5942, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00590-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A DNA Prime-Modified Vaccinia Virus Ankara Boost Vaccine Encoding Thrombospondin-Related Adhesion Protein but Not Circumsporozoite Protein Partially Protects Healthy Malaria-Naive Adults against Plasmodium falciparum Sporozoite Challenge

S. J. Dunachie,1* M. Walther,1 J. E. Epstein,2 S. Keating,1 T. Berthoud,1 L. Andrews,1 R. F. Andersen,1 P. Bejon,1 N. Goonetilleke,1 I. Poulton,1 D. P. Webster,1 G. Butcher,3 K. Watkins,1 R. E. Sinden,3 G. L. Levine,2 T. L. Richie,2 J. Schneider,4 D. Kaslow,5 S. C. Gilbert,1 D. J. Carucci,2 and A. V. S. Hill1

Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom,1 Malaria Program, Naval Medical Research Center, Silver Spring, Maryland,2 Imperial College London, South Kensington, London, United Kingdom,3 Oxxon Therapeutics, Oxford, United Kingdom,4 Vical, Inc., San Diego, California5

Received 10 April 2006/ Accepted 17 July 2006

The safety, immunogenicity, and efficacy of DNA and modified vaccinia virus Ankara (MVA) prime-boost regimes were assessed by using either thrombospondin-related adhesion protein (TRAP) with a multiple-epitope string ME (ME-TRAP) or the circumsporozoite protein (CS) of Plasmodium falciparum. Sixteen healthy subjects who never had malaria (malaria-naive subjects) received two priming vaccinations with DNA, followed by one boosting immunization with MVA, with either ME-TRAP or CS as the antigen. Immunogenicity was assessed by ex vivo gamma interferon (IFN-{gamma}) enzyme-linked immunospot assay (ELISPOT) and antibody assay. Two weeks after the final vaccination, the subjects underwent P. falciparum sporozoite challenge, with six unvaccinated controls. The vaccines were well tolerated and immunogenic, with the DDM-ME TRAP regimen producing stronger ex vivo IFN-{gamma} ELISPOT responses than DDM-CS. One of eight subjects receiving the DDM-ME TRAP regimen was completely protected against malaria challenge, with this group as a whole showing significant delay to parasitemia compared to controls (P = 0.045). The peak ex vivo IFN-{gamma} ELISPOT response in this group correlated strongly with the number of days to parasitemia (P = 0.033). No protection was observed in the DDM-CS group. Prime-boost vaccination with DNA and MVA encoding ME-TRAP but not CS resulted in partial protection against P. falciparum sporozoite challenge in the present study.

* Corresponding author. Mailing address: University of Oxford, Nuffield Department of Clinical Medicine, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Old Rd., Headington, Oxford OX3 7LJ, United Kingdom. Phone: 44(0)1865 857445. Fax: 44(0)1865 857471. E-mail: susie.dunachie{at}ndm.ox.ac.uk.

Editor: W. A. Petri, Jr.

Infection and Immunity, October 2006, p. 5933-5942, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00590-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kaba, S. A., Brando, C., Guo, Q., Mittelholzer, C., Raman, S., Tropel, D., Aebi, U., Burkhard, P., Lanar, D. E. (2009). A Nonadjuvanted Polypeptide Nanoparticle Vaccine Confers Long-Lasting Protection against Rodent Malaria. J. Immunol. 183: 7268-7277 [Abstract] [Full Text]  
  • de Alencar, B. C. G., Persechini, P. M., Haolla, F. A., de Oliveira, G., Silverio, J. C., Lannes-Vieira, J., Machado, A. V., Gazzinelli, R. T., Bruna-Romero, O., Rodrigues, M. M. (2009). Perforin and Gamma Interferon Expression Are Required for CD4+ and CD8+ T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination. Infect. Immun. 77: 4383-4395 [Abstract] [Full Text]  
  • Yoshida, S., Kawasaki, M., Hariguchi, N., Hirota, K., Matsumoto, M. (2009). A Baculovirus Dual Expression System-Based Malaria Vaccine Induces Strong Protection against Plasmodium berghei Sporozoite Challenge in Mice. Infect. Immun. 77: 1782-1789 [Abstract] [Full Text]  
  • Blackwell, J. M., Jamieson, S. E., Burgner, D. (2009). HLA and Infectious Diseases. Clin. Microbiol. Rev. 22: 370-385 [Abstract] [Full Text]  
  • Jeyanathan, M., Mu, J., Kugathasan, K., Zhang, X., Damjanovic, D., Small, C., Divangahi, M., Petrof, B. J., Hogaboam, C. M., Xing, Z. (2008). Airway Delivery of Soluble Mycobacterial Antigens Restores Protective Mucosal Immunity by Single Intramuscular Plasmid DNA Tuberculosis Vaccination: Role of Proinflammatory Signals in the Lung. J. Immunol. 181: 5618-5626 [Abstract] [Full Text]  
  • Bansal, A., Jackson, B., West, K., Wang, S., Lu, S., Kennedy, J. S., Goepfert, P. A. (2008). Multifunctional T-Cell Characteristics Induced by a Polyvalent DNA Prime/Protein Boost Human Immunodeficiency Virus Type 1 Vaccine Regimen Given to Healthy Adults Are Dependent on the Route and Dose of Administration. J. Virol. 82: 6458-6469 [Abstract] [Full Text]  
  • Sanderson, F., Andrews, L., Douglas, A. D., Hunt-Cooke, A., Bejon, P., Hill, A. V. S. (2008). Blood-stage Challenge for Malaria Vaccine Efficacy Trials: A Pilot Study with Discussion of Safety and Potential Value. Am J Trop Med Hyg 78: 878-883 [Abstract] [Full Text]  
  • Huaman, M. C., Martin, L. B., Malkin, E., Narum, D. L., Miller, L. H., Mahanty, S., Long, C. A. (2008). Ex Vivo Cytokine and Memory T Cell Responses to the 42-kDa Fragment of Plasmodium falciparum Merozoite Surface Protein-1 in Vaccinated Volunteers. J. Immunol. 180: 1451-1461 [Abstract] [Full Text]  
  • IMOUKHUEDE, E. B., ANDREWS, L., MILLIGAN, P., BERTHOUD, T., BOJANG, K., NWAKANMA, D., ISMAILI, J., BUCKEE, C., NJIE, F., KEITA, S., SOWE, M., LANG, T., GILBERT, S. C., GREENWOOD, B. M., HILL, A. V. S. (2007). LOW-LEVEL MALARIA INFECTIONS DETECTED BY A SENSITIVE POLYMERASE CHAIN REACTION ASSAY AND USE OF THIS TECHNIQUE IN THE EVALUATION OF MALARIA VACCINES IN AN ENDEMIC AREA. Am J Trop Med Hyg 76: 486-493 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»