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

Sally Sharpe*, Tomás Hanke, Anne Tinsley-Bown, Michael Dennis, Stuart Dowall, Andrew McMichael, Martin Cranage

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

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 μm 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.

Original languageEnglish
Pages (from-to)13-21
Number of pages9
JournalVirology
Volume313
Issue number1
DOIs
Publication statusPublished - 15 Aug 2003

Bibliographical note

Funding Information:
We are grateful to Barry Dowsett for electron microscopy, Roger Hewson for transfection studies, Natasha Polyanskaya for purifying cells from gut tissue, and David Watkins (Wisconsin RPRC) for Mamu tissue typing. This work was supported by the UK Department of Health and the Medical Research Council. The views expressed in the publication are those of the authors and not necessarily those of the Department of Health.

Keywords

  • CTL
  • DNA
  • HIV
  • MVA
  • Macaque
  • Microparticles
  • Multiepitope
  • Vaccine

Fingerprint

Dive into the research topics of 'Mucosal immunization with PLGA-microencapsulated DNA primes a SIV-specific CTL response revealed by boosting with cognate recombinant modified vaccinia virus Ankara'. Together they form a unique fingerprint.

Cite this