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Journal of Virology, October 1998, p. 7846-7851, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Env-Independent Protection Induced by Live, Attenuated Simian Immunodeficiency Virus Vaccines

Björn R. Gundlach,1 Stefan Reiprich,1 Sieghart Sopper,2 Robert E. Means,3 Ulf Dittmer,4 Kerstin Mätz-Rensing,4 Christiane Stahl-Hennig,4 and Klaus Überla1,*

Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Erlangen,1 Institut für Virologie und Immunbiologie, Universität Würzburg, Würzburg,2 and Deutsches Primaten Zentrum, Göttingen,4 Germany, and New England Regional Primate Center, Southborough, Massachusetts3

Received 2 April 1998/Accepted 2 July 1998

Live attenuated simian immunodeficiency viruses (SIV), such as nef deletion mutants, are the most effective vaccines tested in the SIV-macaque model so far. To modulate the antiviral immune response induced by live attenuated SIV vaccines, we had previously infected rhesus monkeys with a nef deletion mutant of SIV expressing interleukin 2 (SIV-IL2) (B. R. Gundlach, H. Linhart, U. Dittmer, S. Sopper, S. Reiprich, D. Fuchs, B. Fleckenstein, G. Hunsmann, S. Stahl-Hennig, and K. Überla, J. Virol. 71:2225-2232, 1997). In the present study, SIV-IL2-infected macaques and macaques infected with the nef deletion mutant SIVDelta NU were challenged with pathogenic SIV 9 to 11 months postvaccination. In contrast to the results with naive control monkeys, no challenge virus could be isolated from the SIV-IL2- and SIVDelta NU-infected macaques. However, challenge virus sequences could be detected by nested PCR in some of the vaccinated macaques. To determine the role of immune responses directed against Env of SIV, four vaccinated macaques were rechallenged with an SIV-murine leukemia virus (MLV) hybrid in which the env gene of SIV had been functionally replaced by the env gene of amphotropic MLV. All vaccinated macaques were protected from productive infection with the SIV-MLV hybrid in the absence of measurable neutralizing antibodies, while two naive control monkeys were readily infected. Since the SIV-MLV hybrid uses the MLV Env receptor Pit2 and not CD4 and a coreceptor for virus entry, chemokine inhibition and receptor interference phenomena were not involved in protection. These results indicate that the protective responses induced by live attenuated SIV vaccines can be independent of host immune reactions directed against Env.

* Corresponding author. Present address: Institut für Virologie, Liebigstr. 24, D-04103 Leipzig, Germany. Phone: 49-341-9714314. Fax: 49-341-9714309. E-mail: ueberla{at}medizin.uni-leipzig.de.

Journal of Virology, October 1998, p. 7846-7851, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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