Comparative evaluation of oral and intranasal priming with replication-competent adenovirus 5 host range mutant (Ad5hr)-simian immunodeficiency virus (SIV) recombinant vaccines on immunogenicity and protective efficacy against SIV(mac251).
Oral, replication-competent Ad-HIV vaccines are advancing to human trials. Previous evaluation of protective efficacy in non-human primates has primarily followed upper respiratory tract administrations. Here we compared sequential oral (O/O) versus intranasal/oral (I/O) priming of rhesus macaques with Ad5 host range mutant-SIV recombinants expressing SIV env/rev, gag, and nef genes followed by boosting with SIV gp120 protein. Cellular immune responses in PBMC were stronger and more frequent after I/O administration. Both groups developed mucosal immunity, including memory cells in bronchial alveolar lavage, and gut-homing receptors on PBMC. Following intrarectal SIV(mac251) challenge, both groups exhibited equivalent, significant protection and robust post-challenge cellular immunity. Our results illustrate the promise of oral replication-competent Ad-recombinant vaccines. Pre-challenge PBMC ELISPOT and proliferative responses did not predict protection in the O/O group, highlighting the need for simple, non-invasive methods to reliably assess mucosal immunity.
Zhou
Qifeng
Q
Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, United States.
Hidajat
Rachmat
R
Peng
Bo
B
Venzon
David
D
Aldrich
M Kristine
MK
Richardson
Ersell
E
Lee
Eun Mi
EM
Kalyanaraman
V S
VS
Grimes
George
G
Gómez-Román
V Raúl
VR
Summers
L Ebonita
LE
Malkevich
Nina
N
Robert-Guroff
Marjorie
M
D000256:Adenoviridae / Q000235:genetics*; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D004261:DNA Replication / Q000235:genetics*; D005243:Feces / Q000821:virology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D016023:Integrins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D009154:Mutation / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*; D013607:Tablets; D014614:Vaccines, Synthetic
D016023:Integrins; D011994:Recombinant Proteins; D018449:SAIDS Vaccines; D013607:Tablets; D014614:Vaccines, Synthetic; D007371:Interferon-gamma