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Clin. Vaccine Immunol. doi:10.1128/CVI.00363-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A DNA vaccine construct incorporating intercellular trafficking and intracellular targeting motifs effectively primes and induces memory B and T cell responses in outbred animals

Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, 99164; Animal Health & Biomedical Sciences, University of Wisconsin-Madison, Madison, WI, 53706; Institute of Animal Health, Compton, UK; Retrovirus Research Unit, RIKEN, Wako, Saitama 351-0198, Japan

^* To whom correspondence should be addressed. Email: wmwangi{at}cvm.tamu.edu.

	Abstract

We developed a vaccine construct in which a BVP22 domain and invariant chain MHC class II-targeting motif, capable of enhancing dendritic cell antigen uptake and presentation, was fused to a sequence encoding a B and T cell antigen from the Anaplasma marginale major surface protein-1a and tested whether this would prime and expand immune responses in outbred calves. A single inoculation using this construct effectively primed immune responses as demonstrated by significant enhancement of CD4⁺ T cell proliferation as compared to calves identically inoculated but with a DNA construct lacking the targeting domains or to calves inoculated with empty vector. These proliferative responses were mirrored by priming and expansion of IFN-⁺CD4⁺ T cells and IgG responses against the linked B cell epitope. Priming by the single immunization induced memory that underwent rapid recall following re-exposure to antigen. These results demonstrate that DNA vaccines targeting key intercellular and intracellular events significantly enhance priming and expansion and support the feasibility of single dose DNA immunization in outbred populations.

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