Protection by attenuated simian immunodeficiency virus in macaques against challenge with virus-infected cells

Almond, Neil; Kent, Karen; Cranage, Martin; Rud, Erling W.; Clarke, Berwyn; Ej, Stott

doi:10.1016/s0140-6736(95)92540-6

Cited by 208 publications

(133 citation statements)

References 9 publications

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“…This study is part of a series that has characterized the early protection against superinfection conferred by inoculation with live nef-attenuated SIVmacC8 (3,5,48,(50)(51)(52). Previously, we showed that protection against acute superinfection with pathogenic, wild-type SIVmacJ5 can be obtained within 21 days of inoculation with live attenuated SIVmacC8, at a time when neutralizing antibodies were not present and limited CD8 ϩ T lymphocyte responses were detected (51).…”

Section: Discussionmentioning

confidence: 99%

“…Live attenuated SIV vaccines can confer effective protection against detectable superinfection with pathogenic, wild-type SIV (3,13,14,29,58,59) and SIV/HIV-1 chimeric virus (7,18,46). Yet there are limits to the breadth of this protection, and live attenuated SIV vaccines have failed to protect against certain heterologous challenge viruses or failed to protect against a challenge performed several years postinoculation (22,31,58).…”

mentioning

confidence: 99%

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CD8 ⁺ Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

Stebbings¹,

Berry²,

Waldmann

et al. 2005

J Virol

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In order to test the hypothesis that CD8 ؉ cytotoxic T lymphocytes mediate protection against acute superinfection, we depleted >99% of CD8 ؉ lymphocytes in live attenuated simian immunodeficiency virus macC8 (SIVmacC8) vaccinees from the onset of vaccination, maintained that depletion for 20 days, and then challenged with pathogenic, wild-type SIVmacJ5. Vaccinees received 5 mg per kg of humanized anti-CD8 monoclonal antibody (MAb) 1 h before inoculation, followed by the same dose again on days 3, 7, 10, 13, and 17. On day 13, peripheral CD8 ؉ T lymphocytes were >99% depleted in three out of four anti-CD8 MAb-treated vaccinees. At this time attenuated SIVmacC8 viral RNA loads in anti-CD8 MAb-treated vaccinees were significantly higher than control vaccinees treated contemporaneously with nonspecific human immunoglobulin. Lymphoid tissue CD8 ؉ T lymphocyte depletion was >99% in three out of four anti-CD8 MAb-treated vaccinees on the day of wild-type SIVmacJ5 challenge. All four control vaccinees and three out of four anti-CD8 MAb-treated vaccinees were protected against detectable superinfection with wild-type SIVmacJ5. Although superinfection with wild-type SIVmacJ5 was detected at postmortem in a single anti-CD8 MAb-treated vaccinee, this did not correlate with the degree of preceding CD8 ؉ T lymphocyte depletion. Clearance of attenuated SIVmacC8 viremia coincided with recovery of normal CD8 ؉ T lymphocyte counts between days 48 and 76. These results support the view that cytotoxic T lymphocytes are important for host-mediated control of SIV primary viremia but do not indicate a central role in protection against acute superinfection conferred by inoculation with live attenuated SIV.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

CD8 ⁺ Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

Stebbings¹,

Berry²,

Waldmann

et al. 2005

J Virol

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“…Data strongly supporting the potential of these HIV vaccines have also been obtained by other groups using attenuated viruses in the SIV-macaque model (Daniel et al, 1992 ;Almond et al, 1995 ;Norley et al, 1996). In this context the potential use of attenuated immunodeficiency viruses for immunization of humans against HIV infection can be considered to be controversial.…”

mentioning

confidence: 96%

“…Deletions in the nef gene of SIV (SIV∆nef) have been shown to attenuate replication capacity in vivo (Kestler et al, 1991 ;Rud et al, 1994). Moreover, an infection of rhesus macaques (Macaca mulatta) with SIV∆nef protects the monkeys against challenge with pathogenic SIV (Daniel et al, 1992 ;Almond et al, 1995 ;Norley et al, 1996 ;Stahl-Hennig et al, 1996). Chimeric SIV that expresses the HIV-1 env gene (SHIV) was also found to be apathogenic in macaques (Li et al, 1995 ;Igarashi et al, 1994).…”

mentioning

confidence: 99%

No reactivation of attenuated immunodeficiency viruses in rhesus macaques after vaccinia virus-induced immune activation.

Dittmer

Nisslein

Meyerhans

et al. 1997

Journal of General Virology

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Live-attenuated simian immunodeficiency virus (SIV) protects macaques against challenge with pathogenic SIV. To evaluate the safety of such vaccines, an investigation of whether or not nefdeleted SIV could be reactivated in vivo by immune activation of the host was conducted. In addition, monkeys infected with apathogenic SIV/HIV-1 chimeric viruses, and two control monkeys that had suppressed replication of pathogenic SIV were examined. During the infection virus became undetectable or persisted at a low level of replication in all monkeys. At this time-point 11 monkeys were immune-activated by a vaccinia virus (VV) superinfection. After VV infection up to 80 % of their lymphocytes showed expression of the activation markers CD25 and CD69 over 2 weeks. However, only the two non-progressing monkeys infected with pathogenic SIV showed a noticeable but transient enhancement of SIV replication and increased SIV antibody titres. By contrast, in monkeys infected with apathogenic immunodeficiency viruses no change in virus load was observed. Therefore, attenuated immunodeficiency viruses cannot be reactivated in vivo by a VV-induced immune activation.In recent years several vaccination strategies against human immunodeficiency virus (HIV) have been evaluated in the simian immunodeficiency virus (SIV) model for AIDS. By far the most successful vaccines are those based on live-attenuated SIV. These attenuated viruses have a reduced pathogenicity caused primarily by their low replicative capacity in the host.

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“…Live attenuated simian immunodeficiency virus (SIV) 1 strains deleted of the nef region have provided a sterilizing immunity against homologous and heterologous virus challenge in rhesus macaque (1)(2)(3)(4)(5). Unfortunately, the continuous and error-prone replication of the nef-deleted virus gave rise to pathogenic escape mutants (6 -9).…”

mentioning

confidence: 99%

High Attenuation and Immunogenicity of a Simian Immunodeficiency Virus Expressing a Proteolysis-resistant Inhibitor of NF-κB

Quinto

Puca

Greenhouse

et al. 2004

Journal of Biological Chemistry

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NF-B/I B proteins play a major role in the transcriptional regulation of human immunodeficiency virus, type-1 (HIV-1). In the case of simian immunodeficiency virus (SIV) the cellular factors required for the viral transcriptional activation and replication in vivo remain undefined. Here, we demonstrate that the p50/p65 NF-B transcription factors enhanced the Tat-mediated transcriptional activation of SIVmac239. In addition, I B-␣S32/36A, a proteolysis-resistant inhibitor of NF-B, strongly inhibited the Tat-mediated transactivation of SIVmac239. Based on this evidence, we have generated a self-regulatory virus by endowing the genome of SIVmac239 with I B-␣S32/36A; the resulting virus, SIVI B-␣S32/36A, was nef-deleted and expressed the NF-B inhibitor. We show that SIVI B-␣S32/36A was highly and stably attenuated both in cell cultures and in vivo in rhesus macaque as compared with a nef-deleted control virus. Moreover, the high attenuation was associated with a robust immune response as measured by SIVspecific antibody production, tetramer, and intracellular IFN-␥ staining of SIV gag-specific T cells. These results underscore the crucial role of NF-B/I B proteins in the regulation of SIV replication both in cell cultures and in monkeys. Thus, inhibitors of NF-B could efficiently counteract the SIV/HIV replication in vivo and may assist in developing novel approaches for AIDS vaccine and therapy.

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Protection by attenuated simian immunodeficiency virus in macaques against challenge with virus-infected cells

Cited by 208 publications

References 9 publications

CD8 ⁺ Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

CD8 ⁺ Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

No reactivation of attenuated immunodeficiency viruses in rhesus macaques after vaccinia virus-induced immune activation.

High Attenuation and Immunogenicity of a Simian Immunodeficiency Virus Expressing a Proteolysis-resistant Inhibitor of NF-κB

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Protection by attenuated simian immunodeficiency virus in macaques against challenge with virus-infected cells

Cited by 208 publications

References 9 publications

CD8 + Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

CD8 + Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

No reactivation of attenuated immunodeficiency viruses in rhesus macaques after vaccinia virus-induced immune activation.

High Attenuation and Immunogenicity of a Simian Immunodeficiency Virus Expressing a Proteolysis-resistant Inhibitor of NF-κB

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Resources

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CD8 ⁺ Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

CD8 ⁺ Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus