AIDS vaccination studies using an ex vivo feline immunodeficiency virus model: failure to protect and possible enhancement of challenge infection by four cell-based vaccines prepared with autologous lymphoblasts.
Immunogenicity and protective activity of four cell-based feline immunodeficiency virus (FIV) vaccines prepared with autologous lymphoblasts were investigated. One vaccine was composed of FIV-infected cells that were paraformaldehyde fixed at the peak of viral expression. The other vaccines were attempts to maximize the expression of protective epitopes that might become exposed as a result of virion binding to cells and essentially consisted of cells mildly fixed after saturation of their surface with adsorbed, internally inactivated FIV particles. The levels of FIV-specific lymphoproliferation exhibited by the vaccinees were comparable to the ones previously observed in vaccine-protected cats, but antibodies were largely directed to cell-derived constituents rather than to truly viral epitopes and had very poor FIV-neutralizing activity. Moreover, under one condition of testing, some vaccine sera enhanced FIV replication in vitro. As a further limit, the vaccines proved inefficient at priming animals for anamnestic immune responses. Two months after completion of primary immunization, the animals were challenged with a low dose of homologous ex vivo FIV. Collectively, 8 of 20 vaccinees developed infection versus one of nine animals mock immunized with fixed uninfected autologous lymphoblasts. After a boosting and rechallenge with a higher virus dose, all remaining animals became infected, thus confirming their lack of protection.
Giannecchini
Simone
S
Retrovirus Center and Virology Section, Department of Biomedicine, University of Pisa, Pisa, Italy.
Isola
Patrizia
P
Sichi
Olimpia
O
Matteucci
Donatella
D
Pistello
Mauro
M
Zaccaro
Lucia
L
Del Mauro
Daniela
D
Bendinelli
Mauro
M
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D002415:Cats; D004195:Disease Models, Animal; D016181:Feline Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D005260:Female; D007117:Immunization, Secondary; D016089:Immunodeficiency Virus, Feline / Q000276:immunology* / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000637:transplantation / Q000821:virology*; D008213:Lymphocyte Activation; D012367:RNA, Viral / Q000097:blood; D014182:Transplantation, Autologous; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D000956:Antigens, Viral; D012367:RNA, Viral; D014765:Viral Vaccines