Journal of Experimental Medicine, Vol 164, 655-660, Copyright © 1986 by Rockefeller University Press

ARTICLES

Genetic control of the immune response in mice to a Plasmodium falciparum sporozoite vaccine. Widespread nonresponsiveness to single malaria T epitope in highly repetitive vaccine

MF Good, JA Berzofsky, WL Maloy, Y Hayashi, N Fujii, WT Hockmeyer and LH Miller

Different H-2 congenic strains of mice were immunized with a P. falciparum sporozoite vaccine currently being tested in humans, or with different segments of the vaccine molecule. Specific IgG production or lymph node cell proliferation in response to different antigens was then determined. Only four of seven strains (representing three of eight possible different class II restriction molecules) responded to the vaccine. Of those restriction molecules, only one, I-Ab, was associated with a response to a malaria-encoded T epitope [contained within NP(NANP)3NA], while the other two molecules (E alpha dE beta d and E alpha kE beta s) were associated with a T cell response to a nonmalarial epitope(s) carboxyterminal to the malaria sequence and encoded by a tetracycline resistance gene, read out of frame. If an analogous situation applies in humans, natural boosting by sporozoites will be very restricted. This has serious implications for the effectiveness of the vaccine, since constant high levels of antisporozoite antibodies and possibly antibody-independent T cell effector functions are required for immunity.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Othoro, C., Johnston, D., Lee, R., Soverow, J., Bystryn, J.-C., Nardin, E. (2009). Enhanced Immunogenicity of Plasmodium falciparum Peptide Vaccines Using a Topical Adjuvant Containing a Potent Synthetic Toll-Like Receptor 7 Agonist, Imiquimod. Infect. Immun. 77: 739-748 [Abstract] [Full Text]  
• Calvo-Calle, J. M., Oliveira, G. A., Watta, C. O., Soverow, J., Parra-Lopez, C., Nardin, E. H. (2006). A Linear Peptide Containing Minimal T- and B-Cell Epitopes of Plasmodium falciparum Circumsporozoite Protein Elicits Protection against Transgenic Sporozoite Challenge. Infect. Immun. 74: 6929-6939 [Abstract] [Full Text]  
• Birkett, A., Lyons, K., Schmidt, A., Boyd, D., Oliveira, G. A., Siddique, A., Nussenzweig, R., Calvo-Calle, J. M., Nardin, E. (2002). A Modified Hepatitis B Virus Core Particle Containing Multiple Epitopes of the Plasmodium falciparum Circumsporozoite Protein Provides a Highly Immunogenic Malaria Vaccine in Preclinical Analyses in Rodent and Primate Hosts. Infect. Immun. 70: 6860-6870 [Abstract] [Full Text]  
• Joshi, M. B., Gam, A. A., Boykins, R. A., Kumar, S., Sacci, J., Hoffman, S. L., Nakhasi, H. L., Kenney, R. T. (2001). Immunogenicity of Well-Characterized Synthetic Plasmodium falciparum Multiple Antigen Peptide Conjugates. Infect. Immun. 69: 4884-4890 [Abstract] [Full Text]  
• Quin, S. J., Langhorne, J. (2001). Different Regions of the Malaria Merozoite Surface Protein 1 of Plasmodium chabaudi Elicit Distinct T-Cell and Antibody Isotype Responses. Infect. Immun. 69: 2245-2251 [Abstract] [Full Text]  
• Hirunpetcharat, C., Vukovic, P., Liu, X. Q., Kaslow, D. C., Miller, L. H., Good, M. F. (1999). Absolute Requirement for an Active Immune Response Involving B Cells and Th Cells in Immunity to Plasmodium yoelii Passively Acquired with Antibodies to the 19-kDa Carboxyl-Terminal Fragment of Merozoite Surface Protein-1. J. Immunol. 162: 7309-7314 [Abstract] [Full Text]  
• Asahi, H., Hernandez, H. J., Stadecker, M. J. (1999). A Novel 62-Kilodalton Egg Antigen from Schistosoma mansoni Induces a Potent CD4+ T Helper Cell Response in the C57BL/6 Mouse. Infect. Immun. 67: 1729-1735 [Abstract] [Full Text]  
• Cavanagh, D. R., Elhassan, I. M., Roper, C., Robinson, V. J., Giha, H., Holder, A. A., Hviid, L., Theander, T. G., Arnot, D. E., McBride, J. S. (1998). A Longitudinal Study of Type-Specific Antibody Responses to Plasmodium falciparum Merozoite Surface Protein-1 in an Area of Unstable Malaria in Sudan. J. Immunol. 161: 347-359 [Abstract] [Full Text]  
• Etlinger, H., Gillessen, D, Lahm, H., Matile, H, Schonfeld, H., Trzeciak, A (1990). Use of prior vaccinations for the development of new vaccines. Science 249: 423-425 [Abstract]  
• Nardin, E., Herrington, D., Davis, J, Levine, M, Stuber, D, Takacs, B, Caspers, P, Barr, P, Altszuler, R, Clavijo, P, al., e. (1989). Conserved repetitive epitope recognized by CD4+ clones from a malaria-immunized volunteer. Science 246: 1603-1606 [Abstract]  
• Hoffman, S., Isenbarger, D, Long, G., Sedegah, M, Szarfman, A, Waters, L, Hollingdale, M., van der Meide, P., Finbloom, D., Ballou, W. (1989). Sporozoite vaccine induces genetically restricted T cell elimination of malaria from hepatocytes. Science 244: 1078-1081 [Abstract]  
• Lowell, G., Ballou, W., Smith, L., Wirtz, R., Zollinger, W., Hockmeyer, W. (1988). Proteosome-lipopeptide vaccines: enhancement of immunogenicity for malaria CS peptides. Science 240: 800-802 [Abstract]  
• Good, M., Maloy, W., Lunde, M., Margalit, H, Cornette, J., Smith, G., Moss, B, Miller, L., Berzofsky, J. (1987). Construction of synthetic immunogen: use of new T-helper epitope on malaria circumsporozoite protein. Science 235: 1059-1062 [Abstract]  
• Miller, L., Howard, R., Carter, R, Good, M., Nussenzweig, V, Nussenzweig, R. (1986). Research toward malaria vaccines. Science 234: 1349-1356 [Abstract]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS