Gag-specific immune enhancement of lentiviral infection after vaccination with an adenoviral vector in an animal model of AIDS.
The evaluation of vaccine strategies in animal models is essential for the development of a vaccine against HIV. In efficacy trials conducted in non-human primate models of AIDS, vaccines based on adenoviruses compared favourably with other vaccine vectors. To determine whether this strategy could be transposed to another animal model, and by extension, to humans, we have evaluated the efficacy of adenoviral vectors in a natural model of AIDS, infection of the cat by the feline immunodeficiency virus (FIV). Recombinant canine adenoviruses expressing the envelope glycoproteins or the Gag protein of a primary strain of FIV were constructed. Three groups of six cats were immunised twice with vectors expressing FIV antigens or with a vector expressing an irrelevant antigen, green fluorescent protein, by intramuscular and subcutaneous routes. Humoral responses were elicited against the transgene product in 6/6, 3/6 and 0/6 cats after immunisation against green fluorescent protein, Gag or the envelope glycoproteins, respectively. Six weeks after the second administration, cats were challenged by the intraperitoneal route with the homologous strain, and viral burden in plasma was followed by quantitative RT-PCR. Immunisation with FIV antigens did not afford protection. Rather, viral RNA was detected at earlier time points in cats immunised against Gag than in cats immunised with a vector expressing an irrelevant antigen. Such immune-mediated enhancement did not appear to have a long-range impact on viral set point or inversion of the CD4(+)/CD8(+) ratio. Thus, in the feline AIDS model pre-existing immunity against a viral antigen exacerbated acute phase infection.
Klonjkowski
Bernard
B
UMR 1161 Virologie INRA, Afssa, ENVA, 94704 Maisons-Alfort, France.
Klein
Dieter
D
Galea
Sandra
S
Gavard
Françoise
F
Monteil
Martine
M
Duarte
Lidia
L
Fournier
Annie
A
Sayon
Sophie
S
Górna
Kamila
K
Ertl
Reinhard
R
Cordonnier
Nathalie
N
Sonigo
Pierre
P
Eloit
Marc
M
Richardson
Jennifer
J
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016516:CD4-CD8 Ratio; D002415:Cats; D004797:Enzyme-Linked Immunosorbent Assay; D016181:Feline Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D007117:Immunization, Secondary; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012367:RNA, Viral / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D012367:RNA, Viral