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Infection and Immunity, May 2009, p. 1798-1806, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.00470-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Polymeric Linear Peptide Chimeric Vaccine-Induced Antimalaria Immunity Is Associated with Enhanced In Vitro Antigen Loading{triangledown}

Luciana M. Silva-Flannery,1 Monica Cabrera-Mora,1 Megan Dickherber,1 and Alberto Moreno1,2*

Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, Georgia 30329,1 Division of Infectious Diseases, Department of Medicine, Emory University, 954 Gatewood Road, Atlanta, Georgia 303292

Received 15 April 2008/ Returned for modification 27 May 2008/ Accepted 12 February 2009

Immunization of mice with Plasmodium berghei or Plasmodium yoelii synthetic linear peptide chimeras (LPCs) based on the circumsporozoite protein protects against experimental challenge with viable sporozoites. The immunogenicity of LPCs is significantly enhanced by spontaneous polymerization. To better understand the antigenic properties of polymeric antimalarial peptides, we studied the immune responses elicited in mice immunized with a polymer or a monomer of a linear peptide construct specific for P. yoelii and compared the responses of antigen-presenting cells following incubation with both peptide species. Efficient uptake of the polymeric peptide in vitro resulted in higher expression of the coactivation markers CD80, CD40, and CD70 on dendritic cells and higher proinflammatory cytokine production than with the monomeric peptide. Macropinocytosis seems to be the main route used by polymeric peptides internalized by antigen-presenting cells. Spontaneous polymerization of synthetic antimalarial-peptide constructs to target professional antigen-presenting cells shows promise for simple delivery of subunit malaria vaccines.

* Corresponding author. Mailing address: Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329. Phone: (404) 727-8611. Fax: (404) 727-8199. E-mail: alberto.moreno{at}emory.edu

{triangledown} Published ahead of print on 23 February 2009.

Editor: J. F. Urban, Jr.

Infection and Immunity, May 2009, p. 1798-1806, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.00470-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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