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Systemically administered DNA encoding a recombinant human immunodeficiency virus (HIV) derived immunogen effectively primes a cytotoxic T lymphocyte (CTL) response in macaques. In this further pilot study we have evaluated mucosal delivery of DNA as an alternative priming strategy. Plasmid DNA, pTH.HW, encoding a multi-CTL epitope gene, was incorporated into poly(D,L-lactic-co-glycolic acid) microparticles of less than 10 microm in diameter. Five intrarectal immunizations failed to stimulate a circulating vaccine-specific CTL response in 2 Mamu-A*01(+) rhesus macaques. However, 1 week after intradermal immunization with a cognate modified vaccinia virus Ankara vaccine MVA.HW, CTL responses were detected in both animals that persisted until analysis postmortem, 12 weeks after the final boost. In contrast, a weaker and less durable response was seen in an animal vaccinated with the MVA construct alone. Analysis of lymphoid tissues revealed a disseminated CTL response in peripheral and regional lymph nodes but not the spleen of both mucosally primed animals.

Type

Journal article

Journal

Virology

Publication Date

15/08/2003

Volume

313

Pages

13 - 21

Keywords

AIDS Vaccines, Administration, Rectal, Animals, Cytotoxicity Tests, Immunologic, Drug Carriers, Drug Compounding, HIV, Immunization, Secondary, Intestinal Mucosa, Lactic Acid, Lymphoid Tissue, Macaca mulatta, Pilot Projects, Polyglycolic Acid, Polymers, Simian Immunodeficiency Virus, T-Lymphocytes, Cytotoxic, Time Factors, Vaccination, Vaccines, DNA, Vaccinia virus