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Journal of Virology, December 2003, p. 12742-12752, Vol. 77, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.23.12742-12752.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Codelivery of CCR7 Ligands as Molecular Adjuvants Enhances the Protective Immune Response against Herpes Simplex Virus Type 1

Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996,¹ Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, 02-787 Warsaw, Poland²

Received 15 May 2003/ Accepted 25 August 2003

Humoral and cellular immunity, associated with long-term protective immunological memory, defines the efficacy of a given vaccine formulation. However, few vaccines achieve this target without the aid of a suitable adjuvant. Molecular adjuvants in vaccination against infectious agents offer a noninvasive means of enhancing the immune response against target antigens. To examine the potency of two ß-chemokines as immunomodulators, plasmid DNA encoding ß-chemokines CCL19 and CCL21 (CCR7L) was codelivered intranasally with plasmid DNA or recombinant vaccinia virus encoding herpes simplex virus (HSV) gB (HSV-gB) in a prime-and-boost vaccination strategy. This vaccination regimen increased serum and vaginal immunoglobulin G (IgG) and IgA, respectively, as well as the numbers of HSV-gB_498-505 peptide-specific gamma interferon-producing CD8⁺ T cells. Distinctively, a high number of cytotoxic T lymphocytes was achieved when pCCR7L was applied at both prime and boost as opposed to omission of pCCR7L. A rapid-recall response was induced in the genital tract upon challenge with the HSV McKrae strain, affording a high level of protection and survival of vaccinated mice. Our results demonstrate that high innate immune kinetics and distribution of adaptive response induced in the nasal mucosa appears to be key factors in generating protective memory responses against HSV. Thus CCR7L expressed ectopically may serve as a molecular adjuvant to boost the immune response to a codelivered antigen in mucosal surfaces.

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