Oral immunization of rhesus macaques with adenoviral HIV vaccines using enteric-coated capsules.
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-gamma-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.
Mercier
George T
GT
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital, Texas Children's Hospital, Houston, TX, USA.
Nehete
Pramod N
PN
Passeri
Marco F
MF
Nehete
Bharti N
BN
Weaver
Eric A
EA
Templeton
Nancy Smyth
NS
Schluns
Kimberly
K
Buchl
Stephanie S
SS
Sastry
K Jagannadha
KJ
Barry
Michael A
MA
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology* / Q000493:pharmacokinetics; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002214:Capsules / Q000008:administration & dosage / Q000493:pharmacokinetics; D004339:Drug Compounding / Q000379:methods*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000032:analysis; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007422:Intestines / Q000276:immunology; D008253:Macaca mulatta; D011109:Polymethacrylic Acids / Q000378:metabolism; D012463:Saliva / Q000276:immunology; D044967:Serum / Q000276:immunology; D013608:Tablets, Enteric-Coated / Q000008:administration & dosage / Q000493:pharmacokinetics; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014621:Vagina / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D002214:Capsules; D000939:Epitopes; D015483:HIV Antibodies; D007070:Immunoglobulin A; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; D022223:Vaccines, Subunit; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus; C030613:polymethacrylic acid; D007371:Interferon-gamma