Pathogenicity of live, attenuated SIV after mucosal infection of neonatal macaques.
Adult macaques do not develop disease after infection with a nef deletion mutant of the simian immunodeficiency virus (SIV) and are protected against challenge with pathogenic virus. This finding led to the proposal to use nef-deleted viruses as live, attenuated vaccines to prevent human acquired immunodeficiency syndrome (AIDS). In contrast, neonatal macaques developed persistently high levels of viremia after oral exposure to and SIV nef, vpr, and negative regulatory element (NRE) deletion mutant. Severe hemolytic anemia, thrombocytopenia, and CD4+ T cell depletion were observed, indicating that neither nef nor vpr determine pathogenicity in neonates. Because such constructs have retained their pathogenic potential, they should not be used as candidate live, attenuated virus vaccines against human AIDS.
Baba
T W
TW
Department of Pediatrics, Tufts University School of Medicine, Boston, MA 02111.
Jeong
Y S
YS
Pennick
D
D
Bronson
R
R
Greene
M F
MF
Ruprecht
R M
RM
D016915:AIDS Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology* / Q000821:virology; D001483:Base Sequence; D015693:Gene Products, nef / Q000235:genetics; D016336:Gene Products, vpr / Q000235:genetics; D008253:Macaca mulatta / Q000276:immunology; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000276:immunology; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology; D014779:Virus Replication / Q000235:genetics
D016915:AIDS Vaccines; D015693:Gene Products, nef; D016336:Gene Products, vpr; D014613:Vaccines, Attenuated