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).

Autor: Zhou Q; Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, United States., Hidajat R, Peng B, Venzon D, Aldrich MK, Richardson E, Lee EM, Kalyanaraman VS, Grimes G, Gómez-Román VR, Summers LE, Malkevich N, Robert-Guroff M
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2007 Nov 19; Vol. 25 (47), pp. 8021-35. Date of Electronic Publication: 2007 Sep 29.
DOI: 10.1016/j.vaccine.2007.09.017
Abstrakt: 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.
Databáze: MEDLINE