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Protection by live, attenuated simian immunodeficiency virus against heterologous challenge.

Publication ,  Journal Article
Wyand, MS; Manson, K; Montefiori, DC; Lifson, JD; Johnson, RP; Desrosiers, RC
Published in: J Virol
October 1999

We examined the ability of a live, attenuated deletion mutant of simian immunodeficiency virus (SIV), SIVmac239Delta3, which is missing nef and vpr genes, to protect against challenge by heterologous strains SHIV89.6p and SIVsmE660. SHIV89.6p is a pathogenic, recombinant SIV in which the envelope gene has been replaced by a human immunodeficiency virus type 1 envelope gene; other structural genes of SHIV89.6p are derived from SIVmac239. SIVsmE660 is an uncloned, pathogenic, independent isolate from the same primate lentivirus subgrouping as SIVmac but with natural sequence variation in all structural genes. The challenge with SHIV89.6p was performed by the intravenous route 37 months after the time of vaccination. By the criteria of CD4(+) cell counts and disease, strong protection against the SHIV89.6p challenge was observed in four of four vaccinated monkeys despite the complete mismatch of env sequences. However, SHIV89.6p infection was established in all four previously vaccinated monkeys and three of the four developed fluctuating viral loads between 300 and 10,000 RNA copy equivalents per ml of plasma 30 to 72 weeks postchallenge. When other vaccinated monkeys were challenged with SIVsmE660 at 28 months after the time of vaccination, SIV loads were lower than those observed in unvaccinated controls but the level of protection was less than what was observed against SHIV89.6p in these experiments and considerably less than the level of protection against SIVmac251 observed in previous experiments. These results demonstrate a variable level of vaccine protection by live, attenuated SIVmac239Delta3 against heterologous virus challenge and suggest that even live, attenuated vaccine approaches for AIDS will face significant hurdles in providing protection against the natural variation present in field strains of virus. The results further suggest that factors other than anti-Env immune responses can be principally responsible for the vaccine protection by live, attenuated SIV.

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Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

October 1999

Volume

73

Issue

10

Start / End Page

8356 / 8363

Location

United States

Related Subject Headings

  • Virology
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • SAIDS Vaccines
  • Macaca mulatta
  • Humans
  • Genes, vpr
  • Genes, nef
  • Gene Deletion
 

Citation

APA
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Wyand, M. S., Manson, K., Montefiori, D. C., Lifson, J. D., Johnson, R. P., & Desrosiers, R. C. (1999). Protection by live, attenuated simian immunodeficiency virus against heterologous challenge. J Virol, 73(10), 8356–8363. https://doi.org/10.1128/JVI.73.10.8356-8363.1999
Wyand, M. S., K. Manson, D. C. Montefiori, J. D. Lifson, R. P. Johnson, and R. C. Desrosiers. “Protection by live, attenuated simian immunodeficiency virus against heterologous challenge.J Virol 73, no. 10 (October 1999): 8356–63. https://doi.org/10.1128/JVI.73.10.8356-8363.1999.
Wyand MS, Manson K, Montefiori DC, Lifson JD, Johnson RP, Desrosiers RC. Protection by live, attenuated simian immunodeficiency virus against heterologous challenge. J Virol. 1999 Oct;73(10):8356–63.
Wyand, M. S., et al. “Protection by live, attenuated simian immunodeficiency virus against heterologous challenge.J Virol, vol. 73, no. 10, Oct. 1999, pp. 8356–63. Pubmed, doi:10.1128/JVI.73.10.8356-8363.1999.
Wyand MS, Manson K, Montefiori DC, Lifson JD, Johnson RP, Desrosiers RC. Protection by live, attenuated simian immunodeficiency virus against heterologous challenge. J Virol. 1999 Oct;73(10):8356–8363.

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

October 1999

Volume

73

Issue

10

Start / End Page

8356 / 8363

Location

United States

Related Subject Headings

  • Virology
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • SAIDS Vaccines
  • Macaca mulatta
  • Humans
  • Genes, vpr
  • Genes, nef
  • Gene Deletion