Multiclade human immunodeficiency virus type 1 envelope immunogens elicit broad cellular and humoral immunity in rhesus monkeys.
The development of a human immunodeficiency virus type 1 (HIV-1) vaccine that elicits potent cellular and humoral immune responses recognizing divergent strains of HIV-1 will be critical for combating the global AIDS epidemic. The present studies were initiated to examine the magnitude and breadth of envelope (Env)-specific T-lymphocyte and antibody responses generated by vaccines containing either a single or multiple genetically distant HIV-1 Env immunogens. Rhesus monkeys were immunized with DNA prime-recombinant adenovirus boost vaccines encoding a Gag-Pol-Nef polyprotein in combination with either a single Env or a mixture of clade-A, clade-B, and clade-C Envs. Monkeys receiving the multiclade Env immunization developed robust immune responses to all vaccine antigens and, importantly, a greater breadth of Env recognition than monkeys immunized with vaccines including a single Env immunogen. All groups of vaccinated monkeys demonstrated equivalent immune protection following challenge with the pathogenic simian-human immunodeficiency virus 89.6P. These data suggest that a multicomponent vaccine encoding Env proteins from multiple clades of HIV-1 can generate broad Env-specific T-lymphocyte and antibody responses without antigenic interference. This study demonstrates that it is possible to generate protective immune responses by vaccination with genetically diverse isolates of HIV-1.
Seaman
Michael S
MS
Beth Israel Deaconess Medical Center, Division of Viral Pathogenesis, 330 Brookline Ave./RE-113, Boston, MA 02215, USA.
Xu
Ling
L
Beaudry
Kristin
K
Martin
Kristi L
KL
Beddall
Margaret H
MH
Miura
Ayako
A
Sambor
Anna
A
Chakrabarti
Bimal K
BK
Huang
Yue
Y
Bailer
Robert
R
Koup
Richard A
RA
Mascola
John R
JR
Nabel
Gary J
GJ
Letvin
Norman L
NL
D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D008253:Macaca mulatta / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D015302:Simian Immunodeficiency Virus / Q000276:immunology
D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D012367:RNA, Viral