Oral immunization of rhesus macaques with adenoviral HIV vaccines using enteric-coated capsules

George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Jagannadha Sastry, Michael A. Barry

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag and a string of six highly-conserved HIV-1 envelope peptides representing broadly cross-reactive CD4+ and CD8+ T cell epitopes. Oral immunization of rhesus macaques with these capsules primed antigen-specific mucosal and systemic immune responses and subsequent intranasal delivery of the envelope peptide cocktail using a mutant cholera toxin adjuvant boosted cellular immune responses including, antigen-specific intracellular IFN-γ-producing CD4+ and CD8+ effector memory T cells in the intestine. These results suggest that the combination of oral adenoviral vector priming followed by intranasal protein/peptide boosting may be an effective mucosal HIV vaccination strategy for targeting viral antigens to the GI tract and priming systemic and mucosal immunity.

Original languageEnglish (US)
Pages (from-to)8687-8701
Number of pages15
JournalVaccine
Volume25
Issue number52
DOIs
StatePublished - Dec 17 2007

Keywords

  • Adenoviral vectors
  • Enteric coatings
  • HIV-1 peptides
  • Mucosal vaccination
  • Oral delivery

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Oral immunization of rhesus macaques with adenoviral HIV vaccines using enteric-coated capsules'. Together they form a unique fingerprint.

  • Cite this

    Mercier, G. T., Nehete, P. N., Passeri, M. F., Nehete, B. N., Weaver, E. A., Templeton, N. S., Schluns, K., Buchl, S. S., Sastry, K. J., & Barry, M. A. (2007). Oral immunization of rhesus macaques with adenoviral HIV vaccines using enteric-coated capsules. Vaccine, 25(52), 8687-8701. https://doi.org/10.1016/j.vaccine.2007.10.030