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Env-independent protection induced by live, attenuated simian immunodeficiency virus vaccines
B R Gundlach1, S Reiprich, S Sopper
1Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Erlangen, Germany.
Abstract:
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. Uberla, J. Virol. 71:2225-2232, 1997). In the present study, SIV-IL2-infected macaques and macaques infected with the nef deletion mutant SIVDeltaNU 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 SIVDeltaNU-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.
Insights
Live attenuated simian immunodeficiency virus (SIV) vaccines, including SIV-IL2 and SIVDeltaNU, protected macaques from pathogenic SIV challenge. This protection was observed even without antibodies targeting the SIV Env protein, suggesting alternative immune mechanisms are involved.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- Live attenuated simian immunodeficiency virus (SIV) vaccines, particularly nef deletion mutants, are highly effective in the SIV-macaque model.
- Previous studies involved infecting rhesus monkeys with SIV expressing interleukin 2 (SIV-IL2) to modulate immune responses.
Purpose of the Study:
- To evaluate the protective efficacy of live attenuated SIV vaccines (SIV-IL2 and SIVDeltaNU) against pathogenic SIV challenge.
- To investigate the role of anti-Env immune responses in vaccine-induced protection.
Main Methods:
- Rhesus monkeys vaccinated with SIV-IL2 or SIVDeltaNU were challenged with pathogenic SIV.
- A subset of vaccinated macaques was rechallenged with an SIV-murine leukemia virus (MLV) hybrid virus to assess Env-specific immunity.
- Nested PCR was used to detect challenge virus sequences.
Main Results:
- No challenge virus was isolated from SIV-IL2- and SIVDeltaNU-vaccinated macaques post-pathogenic SIV challenge, unlike naive controls.
- Challenge virus sequences were detected by PCR in some vaccinated macaques, indicating incomplete viral control.
- All vaccinated macaques were protected from productive infection by an SIV-MLV hybrid virus, despite lacking neutralizing antibodies against SIV Env.
Conclusions:
- Live attenuated SIV vaccines induce protective immunity against pathogenic SIV challenge in macaques.
- Protection mediated by these vaccines can be independent of host immune responses directed against the SIV Env protein.