Immunization of Macaques with Live Simian Human Immunodeficiency Virus (SHIV) Vaccines Conferred Protection Against AIDS Induced by Homologous and Heterologous SHIVs and Simian Immunodeficiency Virus

Kumar, Anil; Mukherjee, Sampa; Shen, Jing; Buch, Shilpa; Li, Zhuang; Adany, Istvan; Liu, Zhenqian; Zhuge, Wu; Piatak, Michael; Lifson, Jeffrey D.; McClure, Harold M.; Narayan, Opendra

doi:10.1006/viro.2002.1544

Cited by 38 publications

(26 citation statements)

References 84 publications

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“…Among the diverse AIDS vaccine strategies tested to date in animal lentivirus models, attenuated lentivirus vaccines have uniformly provided the highest levels of immunogenicity and protection from disease (25,27,(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). Consequently, we chose to test directly the role of lentiviral envelope variation in vaccine efficacy using our well characterized attenuated EIAV vaccine.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is important to note that the current studies indicating the importance of Env variation as a determinant of vaccine efficacy do not preclude a role for Gag-specific immunity in protective vaccine immunity. In this regard, recent studies using attenuated simian immunodeficiency virus (SIV) or simian/human immunodeficiency virus (SHIV) immunizations in monkeys, followed by SHIV or SIV challenges, respectively, have indicated various levels of protection that are apparently independent of the variant Env in the challenge virus (45)(46)(47)(48). Combining the results of vaccine studies in the different animal lentivirus models, we propose that the lentiviral Env serves as the primary determinant of vaccine efficacy to virus exposure and that Gag-specific responses are necessary but insufficient to provide optimal vaccine protection.…”

Section: Discussionmentioning

confidence: 99%

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Envelope variation as a primary determinant of lentiviral vaccine efficacy

Craigo

Zhang

Barnes

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Lentiviral envelope antigenic variation and associated immune evasion are believed to present major obstacles to effective vaccine development. Although this perception is widely assumed by the scientific community, there is, to date, no rigorous experimental data assessing the effect of increasing levels of lentiviral Env variation on vaccine efficacy. It is our working hypothesis that Env is, in fact, a primary determinant of vaccine effectiveness. We previously reported that a successful experimental attenuated equine infectious anemia virus vaccine, derived by mutation of the viral S2 accessory gene, provided 100% protection from disease after virulent virus challenge. Here, we sought to comprehensively test our hypothesis by challenging vaccinated animals with proviral strains of defined, increasing Env variation, using variant envelope SU genes that arose naturally during experimental infection of ponies with equine infectious anemia virus. The reference attenuated vaccine combined with these variant Env challenge strains facilitated evaluation of the protection conferred by ancestral immunogens, because the Env of the attenuated vaccine is a direct ancestor to the variant proviral strain Envs. The results demonstrated that ancestral Env proteins did not impart broad levels of protection against challenge. Furthermore, the results displayed a significant inverse linear correlation of Env divergence and protection from disease. This study demonstrates potential obstacles to the use of single isolate ancestral Env immunogens. Finally, these findings reveal that relatively minor Env variation can pose a substantial challenge to lentiviral vaccine immunity, even when attenuated vaccines are used that, to date, achieve the highest levels of vaccine protection.ancestral immunogen ͉ equine infectious anemia virus ͉ lentivirus

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Envelope variation as a primary determinant of lentiviral vaccine efficacy

Craigo

Zhang

Barnes

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…In nature, FIV transmission mainly occurs through bite wounds, although other routes, such as mucosal transmission, are also possible (58). However, sexual transmission is of the utmost importance for HIV, and thus, vaginal or rectal challenges are commonly used to test vaccinal protection in FIV (23), as well as in other animal models (16,40,50,71). Therefore, we examined whether the vaccinees that had resisted intraperitoneal challenge could also resist an intravaginal challenge.…”

Section: Discussionmentioning

confidence: 99%

AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Protection from an Intraclade Challenge Administered Systemically or Mucosally by an Attenuated Vaccine

Pistello

Matteucci

Bonci

et al. 2003

J Virol

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Feline immunodeficiency virus (FIV) infection of domestic cats represents a valuable system through which to investigate criteria for antilentiviral vaccines in a natural host species. Here, we examined whether vaccination with a strain of FIV attenuated as a result of prolonged growth in vitro could protect against a fully virulent, highly heterologous intraclade challenge. The results indicated that the vaccine virus produced a low-grade infection with no detectable pathological effects and afforded a long-lasting sterilizing immunity if the challenge was delivered intraperitoneally as cell-free virus but not against a cell-associated intravaginal challenge. In the latter case, however, the replication and pathological consequences of the challenge virus were markedly suppressed. Together with similar results obtained in rhesus monkey models, these findings should give impulse to the development of attenuated FIV vaccines to be tested in controlled studies in field cats. Field studies may provide answers to some of the existing safety concerns surrounding attenuated AIDS vaccines in humans.

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“…Attenuated SIV strains have been effective at mediating protection against both intravenous and mucosal challenges, resulting in either sterile protection or a solid, long-term suppression of replication of the pathogenic challenge virus strain with prevention of disease progression in most animals (11,24,53,54). Infections with live attenuated SIVs elicit neutralizing antibody (NAb) responses (8,10,27,31,37,54), which have been shown to correlate with protection from a pathogenic challenge (54). However, the passive transfer of serum or immunoglobulin from vaccinated animals has largely been unsuccessful at preventing infection (2,22).…”

Section: Although Live Attenuated Vaccines Can Provide Potent Protectmentioning

confidence: 99%

Effect of CD8 ⁺ Lymphocyte Depletion on Virus Containment after Simian Immunodeficiency Virus SIVmac251 Challenge of Live Attenuated SIVmac239Δ3-Vaccinated Rhesus Macaques

Schmitz

Johnson

McClure

et al. 2005

J Virol

Self Cite

114

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Although live attenuated vaccines can provide potent protection against simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus challenges, the specific immune responses that confer this protection have not been determined. To test whether cellular immune responses mediated by CD8؉ lymphocytes contribute to this vaccine-induced protection, we depleted rhesus macaques vaccinated with the live attenuated virus SIVmac239⌬3 of CD8 ؉ lymphocytes and then challenged them with SIVmac251 by the intravenous route. While vaccination did not prevent infection with the pathogenic challenge virus, the postchallenge levels of virus in the plasmas of vaccinated control animals were significantly lower than those for unvaccinated animals. The depletion of CD8 ؉ lymphocytes at the time of challenge resulted in virus levels in the plasma that were intermediate between those of the vaccinated and unvaccinated controls, suggesting that CD8؉ cell-mediated immune responses contributed to protection. Interestingly, at the time of challenge, animals expressing the Mamu-A*01 major histocompatibility complex class I allele showed significantly higher frequencies of SIV-specific CD8 ؉ T-cell responses and lower neutralizing antibody titers than those in Mamu-A*01 ؊ animals. Consistent with these findings, the depletion of CD8 ؉ lymphocytes abrogated vaccineinduced protection, as judged by the peak postchallenge viremia, to a greater extent in Mamu-A*01 ؉ than in Mamu-A*01 ؊ animals. The partial control of postchallenge viremia after CD8 ؉ lymphocyte depletion suggests that both humoral and cellular immune responses induced by live attenuated SIV vaccines can contribute to protection against a pathogenic challenge and that the relative contribution of each of these responses to protection may be genetically determined.Several unique biological features render human immunodeficiency virus (HIV) infection an especially challenging infection to prevent by vaccination (7,12,34). The development of an AIDS vaccine is further hindered by a lack of information on the types of immune responses that a vaccine should elicit in order to block or limit HIV infection (25). Both clinical observations of HIV-infected humans and experimental data from nonhuman primate models have indicated that antibodies induced by currently available immunogens are unlikely to elicit broadly protective immunity (6, 7). The temporal concordance of emerging virus-specific responses by CD8 ϩ T cells with declining viremia during primary HIV-1 infection (26), together with observations in nonhuman primates demonstrating that the experimental depletion of CD8 ϩ lymphocytes results in striking increases in virus levels (21,45), suggests that the induction of virus-specific cytotoxic T lymphocyte (CTL) responses should be a key objective of vaccine development strategies. However, vaccine approaches that elicit high-frequency virus-specific CTL responses have proven incapable of

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Immunization of Macaques with Live Simian Human Immunodeficiency Virus (SHIV) Vaccines Conferred Protection Against AIDS Induced by Homologous and Heterologous SHIVs and Simian Immunodeficiency Virus

Cited by 38 publications

References 84 publications

Envelope variation as a primary determinant of lentiviral vaccine efficacy

Envelope variation as a primary determinant of lentiviral vaccine efficacy

AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Protection from an Intraclade Challenge Administered Systemically or Mucosally by an Attenuated Vaccine

Effect of CD8 ⁺ Lymphocyte Depletion on Virus Containment after Simian Immunodeficiency Virus SIVmac251 Challenge of Live Attenuated SIVmac239Δ3-Vaccinated Rhesus Macaques

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Immunization of Macaques with Live Simian Human Immunodeficiency Virus (SHIV) Vaccines Conferred Protection Against AIDS Induced by Homologous and Heterologous SHIVs and Simian Immunodeficiency Virus

Cited by 38 publications

References 84 publications

Envelope variation as a primary determinant of lentiviral vaccine efficacy

Envelope variation as a primary determinant of lentiviral vaccine efficacy

AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Protection from an Intraclade Challenge Administered Systemically or Mucosally by an Attenuated Vaccine

Effect of CD8 + Lymphocyte Depletion on Virus Containment after Simian Immunodeficiency Virus SIVmac251 Challenge of Live Attenuated SIVmac239Δ3-Vaccinated Rhesus Macaques

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Effect of CD8 ⁺ Lymphocyte Depletion on Virus Containment after Simian Immunodeficiency Virus SIVmac251 Challenge of Live Attenuated SIVmac239Δ3-Vaccinated Rhesus Macaques