Mucosal immunization with PLGA-microencapsulated DNA primes a SIV-specific CTL response revealed by boosting with cognate recombinant modified vaccinia virus Ankara.

Journal article

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.

Authors: Sharpe, S; Hanke, T; Tinsley-Bown, A; Dennis, M; Dowall, S

• Publication status: Published
• Journal: Virology
• Volume: 313
• Issue: 1
• Pages: 13-21
• Publication date: 2003-08-01
• DOI: 10.1016/s0042-6822(03)00282-4
• EISSN: 1096-0341
• ISSN: 0042-6822
• Language: English
• Keywords: Macaca mulatta; T-Lymphocytes, Cytotoxic; Drug Carriers; Pilot Projects; HIV; AIDS Vaccines; Administration, Rectal; Drug Compounding; Vaccines, DNA; Polymers; Immunization, Secondary; Cytotoxicity Tests, Immunologic; Vaccination; Time Factors; Polyglycolic Acid; Animals; Vaccinia virus; Simian immunodeficiency virus; Lymphoid Tissue; Lactic Acid; Intestinal Mucosa