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Live attenuated,nef-deleted SIV is pathogenic in most adult macaques after prolonged observation

 

作者: Regina Hofmann-Lehmann,   Josef Vlasak,   Alison Williams,   Agnès-Laurence Chenine,   Harold McClure,   Daniel Anderson,   Shawn O'Neil,   Ruth Ruprecht,  

 

期刊: AIDS  (OVID Available online 2003)
卷期: Volume 17, issue 2  

页码: 157-166

 

ISSN:0269-9370

 

年代: 2003

 

出版商: OVID

 

关键词: live attenuated SIV;pathogenicity;AIDS vaccine;primate model;HIV

 

数据来源: OVID

 

摘要:

Objective:A live attenuated SIV vaccine strain, termed SIVmac239Δ3 and containing large deletions innef,vprand the negative regulatory element, was previously shown to cause AIDS mostly in monkeys vaccinated as infants. In the present study, we demonstrate that SIVmac239Δ3 is pathogenic in most vaccinated adult monkeys, given enough time.Methods:Eleven rhesus macaques vaccinated as adults with SIVmac239Δ3 were followed for extended periods (up to 6.8 years).Results:We found signs of immune dysregulation in all 11 adult vaccinees. All animals developed persistently inverted CD4 : CD8 T-cell ratios, seven (64%) had persistent recurrent viremia, and six (55%) had decreased CD4 T-cell counts (< 500 × 106cells/l). Further signs included low CD4CD29 lymphocyte subsets, loss of anti-Gag antibodies, anemia, thrombocytopenia, wasting, and opportunistic infections. Two adult vaccinees (18%) subsequently developed AIDS. Development of chronic, recurrent viremia with plasma viral RNA loads ⩾ 103copies/ml and cytoviremia was a poor prognostic sign.Conclusion:Our data demonstrate that with time, a live attenuated, multiply deleted SIV vaccine can cause immune dysregulation in most vaccine recipients, even in initially immune competent, healthy adults. Immune dysfunction can progress to full AIDS. However, pathogenic effects became evident only several years after vaccination. Thus, mass vaccination of humans with similarly constructed live attenuated HIV vaccines, recently suggested for countries with high HIV-1 transmission rates, seems contraindicated.

 

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