The Journal of Immunology, Vol 155, Issue 4 2039-2046, Copyright © 1995 by American Association of Immunologists

ARTICLES

Complexity of the cytokine and antibody response elicited by immunizing mice with Plasmodium yoelii circumsporozoite protein plasmid DNA

G Mor, DM Klinman, S Shapiro, E Hagiwara, M Sedegah, JA Norman, SL Hoffman and AD Steinberg
Section of Retroviral Immunology, Food and Drug Administration, Bethesda, MD 20892, USA.

The number, type, and location of cytokine- and Ab-secreting cells activated in mice immunized and boosted with plasmid DNA encoding the circumsporozoite protein of the malarial parasite Plasmodium yoelii (PyCSP) were monitored. The initial humoral response was localized to the draining lymph nodes and was characterized by production of IgG1 anti-PyCSP Abs and the Th2 cytokine IL-4. In contrast, the secondary response was dominated by IFN-gamma production (a Th1 cytokine) and the secretion of IgG2a anti-PyCSP Abs in the spleen. PyCSP DNA and mRNA were detected only in the quadriceps muscles (sites of plasmid injection), yet these sites lacked either cytokine- or Ab-secreting cells. These findings indicate that circulating lymphocytes encounter plasmid-encoded Ag in the muscle bed, initiate a humoral response in the draining lymph nodes, and then seed distal lymphoid organs. Profound differences were observed between the primary and secondary immune responses induced by plasmid immunization, which may influence vaccine efficacy.

This article has been cited by other articles:

				H. Shirota, L. Petrenko, C. Hong, and D. M. Klinman Potential of Transfected Muscle Cells to Contribute to DNA Vaccine Immunogenicity J. Immunol., July 1, 2007; 179(1): 329 - 336. [Abstract] [Full Text] [PDF]

				S. Mendez, S. Gurunathan, S. Kamhawi, Y. Belkaid, M. A. Moga, Y. A. W. Skeiky, A. Campos-Neto, S. Reed, R. A. Seder, and D. Sacks The Potency and Durability of DNA- and Protein-Based Vaccines Against Leishmania major Evaluated Using Low-Dose, Intradermal Challenge J. Immunol., April 15, 2001; 166(8): 5122 - 5128. [Abstract] [Full Text] [PDF]

				R. Weiss, W. W. Leitner, S. Scheiblhofer, D. Chen, A. Bernhaupt, S. Mostbock, J. Thalhamer, and J. A. Lyon Genetic Vaccination against Malaria Infection by Intradermal and Epidermal Injections of a Plasmid Containing the Gene Encoding the Plasmodium berghei Circumsporozoite Protein Infect. Immun., October 1, 2000; 68(10): 5914 - 5919. [Abstract] [Full Text] [PDF]

				D. Haddad, J. Ramprakash, M. Sedegah, Y. Charoenvit, R. Baumgartner, S. Kumar, S. L. Hoffman, and W. R. Weiss Plasmid Vaccine Expressing Granulocyte-Macrophage Colony-Stimulating Factor Attracts Infiltrates Including Immature Dendritic Cells into Injected Muscles J. Immunol., October 1, 2000; 165(7): 3772 - 3781. [Abstract] [Full Text] [PDF]

				M. Vercammen, T. Scorza, K. Huygen, J. De Braekeleer, R. Diet, D. Jacobs, E. Saman, and H. Verschueren DNA Vaccination with Genes Encoding Toxoplasma gondii Antigens GRA1, GRA7, and ROP2 Induces Partially Protective Immunity against Lethal Challenge in Mice Infect. Immun., January 1, 2000; 68(1): 38 - 45. [Abstract] [Full Text] [PDF]

				A. A. Belperron, D. Feltquate, B. A. Fox, T. Horii, and D. J. Bzik Immune Responses Induced by Gene Gun or Intramuscular Injection of DNA Vaccines That Express Immunogenic Regions of the Serine Repeat Antigen from Plasmodium falciparum Infect. Immun., October 1, 1999; 67(10): 5163 - 5169. [Abstract] [Full Text] [PDF]

				M. M. Rodrigues, M. Ribeirao, V. Pereira-Chioccola, L. Renia, and F. Costa Predominance of CD4 Th1 and CD8 Tc1 Cells Revealed by Characterization of the Cellular Immune Response Generated by Immunization with a DNA Vaccine Containing a Trypanosoma cruzi Gene Infect. Immun., August 1, 1999; 67(8): 3855 - 3863. [Abstract] [Full Text] [PDF]

				A. Arulkanthan, W. C. Brown, T. C. McGuire, and D. P. Knowles Biased Immunoglobulin G1 Isotype Responses Induced in Cattle with DNA Expressing msp1a of Anaplasma marginale Infect. Immun., July 1, 1999; 67(7): 3481 - 3487. [Abstract] [Full Text] [PDF]

				M. Ichino, G. Mor, J. Conover, W. R. Weiss, M. Takeno, K. J. Ishii, and D. M. Klinman Factors Associated with the Development of Neonatal Tolerance After the Administration of a Plasmid DNA Vaccine J. Immunol., April 1, 1999; 162(7): 3814 - 3818. [Abstract] [Full Text] [PDF]

				N. D. Tolley, I. Tsunoda, and R. S. Fujinami DNA Vaccination against Theiler's Murine Encephalomyelitis Virus Leads to Alterations in Demyelinating Disease J. Virol., February 1, 1999; 73(2): 993 - 1000. [Abstract] [Full Text]

				Adam. D. Cohen, J. D. Boyer, and D. B. Weiner Modulating the immune response to genetic immunization FASEB J, December 1, 1998; 12(15): 1611 - 1626. [Abstract] [Full Text]

				W. R. Weiss, K. J. Ishii, R. C. Hedstrom, M. Sedegah, M. Ichino, K. Barnhart, D. M. Klinman, and S. L. Hoffman A Plasmid Encoding Murine Granulocyte-Macrophage Colony-Stimulating Factor Increases Protection Conferred by a Malaria DNA Vaccine J. Immunol., September 1, 1998; 161(5): 2325 - 2332. [Abstract] [Full Text] [PDF]

				D Verthelyi, N Dybdal, K A Elias, and D M Klinman DNAse treatment does not improve the survival of lupus prone (NZB6NZW)F1 mice Lupus, May 1, 1998; 7(4): 223 - 230. [Abstract] [PDF]

				D. M. Klinman, J. M. G. Sechler, J. Conover, M. Gu, and A. S. Rosenberg Contribution of Cells at the Site of DNA Vaccination to the Generation of Antigen-Specific Immunity and Memory J. Immunol., March 1, 1998; 160(5): 2388 - 2392. [Abstract] [Full Text] [PDF]

				Y. Chen, R. G. Webster, and D. L. Woodland Induction of CD8+ T Cell Responses to Dominant and Subdominant Epitopes and Protective Immunity to Sendai Virus Infection by DNA Vaccination J. Immunol., March 1, 1998; 160(5): 2425 - 2432. [Abstract] [Full Text] [PDF]