The Journal of Immunology, Vol 159, Issue 7 3424-3433, Copyright © 1997 by American Association of Immunologists

ARTICLES

Induction of protective CTL responses against the Plasmodium yoelii circumsporozoite protein by immunization with peptides

ED Franke, G Corradin and SL Hoffman
Naval Medical Research Institute, Malaria Program, Rockville, MD 20852, USA.

To determine the optimum combination, concentration, and formulation of synthetic peptides and adjuvants to induce protective CTL responses against the Plasmodium yoelii circumsporozoite protein (PyCSP), BALB/c mice were immunized with linear and multiple antigen peptides (MAP) including PyCSP CTL and Th epitopes in Montanide's ISA51, Lipofectin, and Lipofectamine. An H-2K(d)-restricted PyCSP CTL epitope, SYVPSAEQI (amino acids (aa) 280-288), recognized by protective CTL clones, was included in the following peptides: a 9-aa linear peptide (SYVPSAEQI; PyCSP9), a 20-aa linear peptide (aa 280-299; SYVPSAEQILEFVKQISSL; PyCSP20), a MAP containing four branches of PyCSP20 (MAP(280-299)), and a linear peptide and a MAP(MAP(280-299)p2p30) in which PyCSP20 was colinearly synthesized with two universal Th epitopes from tetanus toxin (p2p30). A MAP containing the PyCSP Th epitope (aa 57-70; KIYNRNIVNRLLGD) was included in some experiments. The highest specific lytic activity against peptide-pulsed target cells was obtained with splenocytes from mice immunized with three doses at 3-wk intervals of MAP(280-299)p2p30 in Lipofectin or Lipofectamine. Forty percent of the mice immunized with MAP(280-299)p2p30 and Lipofectin were protected against sporozoite challenge. Immunization with CTL and Th epitopes co- linearly synthesized in a MAP induced significantly better CTL than did immunization with the same sequence as a linear peptide, or immunization with a mixture of two individual MAPs, one with the CTL epitope and the second with the Th epitope.

This article has been cited by other articles:

				P. Nava-Parada, G. Forni, K. L. Knutson, L. R. Pease, and E. Celis Peptide Vaccine Given with a Toll-Like Receptor Agonist Is Effective for the Treatment and Prevention of Spontaneous Breast Tumors Cancer Res., February 1, 2007; 67(3): 1326 - 1334. [Abstract] [Full Text] [PDF]

				Y. Osorio, J. Cohen, and H. Ghiasi Improved Protection from Primary Ocular HSV-1 Infection and Establishment of Latency Using Multigenic DNA Vaccines Invest. Ophthalmol. Vis. Sci., February 1, 2004; 45(2): 506 - 514. [Abstract] [Full Text] [PDF]

				D. L. Doolan and S. L. Hoffman The Complexity of Protective Immunity Against Liver-Stage Malaria J. Immunol., August 1, 2000; 165(3): 1453 - 1462. [Abstract] [Full Text] [PDF]

				E. D. Franke, A. Sette, J. Sacci Jr., S. Southwood, G. Corradin, and S. L. Hoffman A Subdominant CD8+ Cytotoxic T Lymphocyte (CTL) Epitope from the Plasmodium yoelii Circumsporozoite Protein Induces CTLs That Eliminate Infected Hepatocytes from Culture Infect. Immun., June 1, 2000; 68(6): 3403 - 3411. [Abstract] [Full Text] [PDF]

				S. M. Lonning, W. Zhang, and T. C. McGuire Gag Protein Epitopes Recognized by CD4+ T-Helper Lymphocytes from Equine Infectious Anemia Virus-Infected Carrier Horses J. Virol., May 1, 1999; 73(5): 4257 - 4265. [Abstract] [Full Text]

				R. Lo-Man, S. Bay, S. Vichier-Guerre, E. Deriaud, D. Cantacuzene, and C. Leclerc A Fully Synthetic Immunogen Carrying a Carcinoma-associated Carbohydrate for Active Specific Immunotherapy1 Cancer Res., April 1, 1999; 59(7): 1520 - 1524. [Abstract] [Full Text] [PDF]

				M. Sedegah, T. R. Jones, M. Kaur, R. Hedstrom, P. Hobart, J. A. Tine, and S. L. Hoffman Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine PNAS, June 23, 1998; 95(13): 7648 - 7653. [Abstract] [Full Text] [PDF]