Priming-boosting vaccination with recombinant Mycobacterium bovis bacillus Calmette-Guérin and a nonreplicating vaccinia virus recombinant leads to long-lasting and effective immunity.
Virus-specific T-cell responses can limit immunodeficiency virus type 1 (HIV-1) transmission and prevent disease progression and so could serve as the basis for an affordable, safe, and effective vaccine in humans. To assess their potential for a vaccine, we used Mycobacterium bovis bacillus Calmette-Guérin (BCG)-Tokyo and a replication-deficient vaccinia virus strain (DIs) as vectors to express full-length gag from simian immunodeficiency viruses (SIVs) (rBCG-SIVgag and rDIsSIVgag). Cynomolgus macaques were vaccinated with either rBCG-SIVgag dermally as a single modality or in combination with rDIsSIVgag intravenously. When cynomologus macaques were primed with rBCG-SIVgag and then boosted with rDIsSIVgag, high levels of gamma interferon (IFN-gamma) spot-forming cells specific for SIV Gag were induced. This combination regimen elicited effective protective immunity against mucosal challenge with pathogenic simian-human immunodeficiency virus for the 1 year the macaques were under observation. Antigen-specific intracellular IFN-gamma activity was similarly induced in each of the macaques with the priming-boosting regimen. Other groups receiving the opposite combination or the single-modality vaccines were not effectively protected. These results suggest that a recombinant M. bovis BCG-based vector may have potential as an HIV/AIDS vaccine when administered in combination with a replication-deficient vaccinia virus DIs vector in a priming-boosting strategy.
Ami
Yasushi
Y
Division of Experimental Animal Research, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.
Izumi
Yasuyuki
Y
Matsuo
Kazuhiro
K
Someya
Kenji
K
Kanekiyo
Masaru
M
Horibata
Shigeo
S
Yoshino
Naoto
N
Sakai
Koji
K
Shinohara
Katsuaki
K
Matsumoto
Sohkichi
S
Yamada
Takeshi
T
Yamazaki
Shudo
S
Yamamoto
Naoki
N
Honda
Mitsuo
M
D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000235:genetics; D002478:Cells, Cultured; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D012900:Smallpox Vaccine / Q000008:administration & dosage* / Q000235:genetics; D013045:Species Specificity; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage
D001500:BCG Vaccine; D015683:Gene Products, gag; D018449:SAIDS Vaccines; D012900:Smallpox Vaccine; D014614:Vaccines, Synthetic; D007371:Interferon-gamma