Systemic immunization with an ALVAC-HIV-1/protein boost vaccine strategy protects rhesus macaques from CD4+ T-cell loss and reduces both systemic and mucosal simian-human immunodeficiency virus SHIVKU2 RNA levels.
Transmission of human immunodeficiency virus type 1 (HIV-1) occurs primarily via the mucosal route, suggesting that HIV-1 vaccines may need to elicit mucosal immune responses. Here, we investigated the immunogenicity and relative efficacy of systemic immunization with two human ALVAC-HIV-1 recombinant vaccines expressing Gag, Pol, and gp120 (vCP250) or Gag, Pol, and gp160 (vCP1420) in a prime-boost protocol with their homologous vaccine native Env proteins. The relative efficacy was measured against a high-dose mucosal exposure to the pathogenic neutralization-resistant variant SHIV(KU2) (simian-human immunodeficiency virus). Systemic immunization with both vaccine regimens decreased viral load levels not only in blood but unexpectedly also in mucosal sites and protected macaques from peripheral CD4+ T-cell loss. This protective effect was stronger when the gp120 antigen was included in the vaccine. Inclusion of recombinant Tat protein in the boosting phase along with the Env protein did not contribute further to the preservation of CD4+ T cells. Thus, systemic immunization with ALVAC-HIV-1 vaccine candidates elicits anti-HIV-1 immune responses able to contain virus replication also at mucosal sites in macaques.
Advanced BioScience Laboratories, Inc., Kensington, Maryland 20895, USA.
Ranajit
R
Pal
David
D
Venzon
Sampa
S
Santra
Vaniambadi S
VS
Kalyanaraman
David C
DC
Montefiori
Lindsey
L
Hocker
Lauren
L
Hudacik
Nicolas
N
Rose
Janos
J
Nacsa
Yvette
Y
Edghill-Smith
Marcin
M
Moniuszko
Zdenek
Z
Hel
Igor M
IM
Belyakov
Jay A
JA
Berzofsky
Robyn Washington
RW
Parks
Phillip D
PD
Markham
Norman L
NL
Letvin
Jim
J
Tartaglia
Genoveffa
G
Franchini
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D018791:CD4 Lymphocyte Count; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D007117:Immunization, Secondary; D008253:Macaca mulatta; D012367:RNA, Viral / Q000032:analysis*; D012107:Research Design; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000302:isolation & purification; D019562:Viral Load; D014766:Viremia / Q000517:prevention & control
D016915:AIDS Vaccines; D015483:HIV Antibodies; D012367:RNA, Viral; C421254:human immunodeficiency virus type 1 Tat vaccine