Summary: Vaccines or candidate vaccines designed to prevent SAIDS; (SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME); and containing inactivated SIMIAN IMMUNODEFICIENCY VIRUS or type D retroviruses or some of their component antigens.
- Muthumani K, Bagarazzi M, Conway D, Hwang D, Manson K, Ciccarelli R, et al. A Gag-Pol/Env-Rev SIV239 DNA vaccine improves CD4 counts, and reduce viral loads after pathogenic intrarectal SIV(mac)251 challenge in rhesus Macaques. Vaccine. 2003;21:629-37 pubmed..Furthermore, vaccinated animals exhibited protection against CD4(+) T-cell loss. ..
- Xiao P, Zhao J, Patterson L, Brocca Cofano E, Venzon D, Kozlowski P, et al. Multiple vaccine-elicited nonneutralizing antienvelope antibody activities contribute to protective efficacy by reducing both acute and chronic viremia following simian/human immunodeficiency virus SHIV89.6P challenge in rhesus macaques. J Virol. 2010;84:7161-73 pubmed publisher..Overall, the replicating Ad5hr-HIV/SIV priming/gp140 protein boosting approach elicited strong systemic and mucosal antibodies with multiple functional activities associated with control of both acute and chronic viremia. ..
- Ahmed R, Nilsson C, Wang Y, Lehner T, Biberfeld G, Thorstensson R. Beta-chemokine production in macaques vaccinated with live attenuated virus correlates with protection against simian immunodeficiency virus (SIVsm) challenge. J Gen Virol. 1999;80 ( Pt 7):1569-74 pubmed..The results indicate that beta-chemokines may play a role in protective immunity but also that genetic and/or environmental factors may influence their production. ..
- Stevceva L, Alvarez X, Lackner A, Tryniszewska E, Kelsall B, Nacsa J, et al. Both mucosal and systemic routes of immunization with the live, attenuated NYVAC/simian immunodeficiency virus SIV(gpe) recombinant vaccine result in gag-specific CD8(+) T-cell responses in mucosal tissues of macaques. J Virol. 2002;76:11659-76 pubmed..We conclude that immunization with a live vector vaccine results in the appearance of CD8(+) T-cell responses at mucosal sites even when the vaccine is delivered by nonmucosal routes. ..
- Horton H, Vogel T, Carter D, Vielhuber K, Fuller D, Shipley T, et al. Immunization of rhesus macaques with a DNA prime/modified vaccinia virus Ankara boost regimen induces broad simian immunodeficiency virus (SIV)-specific T-cell responses and reduces initial viral replication but does not prevent disease progression f. J Virol. 2002;76:7187-202 pubmed..01). However, despite the induction of virus-specific cellular immune responses and reduced peak viral loads, most animals still suffered from gradual CD4 depletion and progressed to disease. ..
- Barouch D, Kunstman J, Kuroda M, Schmitz J, Santra S, Peyerl F, et al. Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes. Nature. 2002;415:335-9 pubmed..These data indicate that viral escape from CTL recognition may be a major limitation of the CTL-based AIDS vaccines that are likely to be administered to large human populations over the next several years. ..
- Staprans S, Barry A, Silvestri G, Safrit J, Kozyr N, Sumpter B, et al. Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein. Proc Natl Acad Sci U S A. 2004;101:13026-31 pubmed..These data suggest suggest that candidate AIDS vaccines may not simply be either efficacious or neutral; they may also have the potential to be harmful. ..
- Titti F, Sernicola L, Geraci A, Panzini G, Di Fabio S, Belli R, et al. Live attenuated simian immunodeficiency virus prevents super-infection by cloned SIVmac251 in cynomolgus monkeys. J Gen Virol. 1997;78 ( Pt 10):2529-39 pubmed
- Reynolds M, Weiler A, Piaskowski S, Piatak M, Robertson H, Allison D, et al. A trivalent recombinant Ad5 gag/pol/nef vaccine fails to protect rhesus macaques from infection or control virus replication after a limiting-dose heterologous SIV challenge. Vaccine. 2012;30:4465-75 pubmed publisher..Our results are consistent with those observed in the Step trial and indicate that SIV immunization and challenge studies in macaque models of HIV infection can be informative in assessing pre-clinical HIV vaccines. ..
- Valentine L, Watkins D. Relevance of studying T cell responses in SIV-infected rhesus macaques. Trends Microbiol. 2008;16:605-11 pubmed publisher..The best animal model available to explore such issues is simian immunodeficiency virus infection of rhesus macaques, which serves as the primary proving ground for AIDS vaccines. ..
- Genesca M, Skinner P, Hong J, Li J, Lu D, McChesney M, et al. With minimal systemic T-cell expansion, CD8+ T Cells mediate protection of rhesus macaques immunized with attenuated simian-human immunodeficiency virus SHIV89.6 from vaginal challenge with simian immunodeficiency virus. J Virol. 2008;82:11181-96 pubmed publisher
- Pahar B, Cantu M, Zhao W, Kuroda M, Veazey R, Montefiori D, et al. Single epitope mucosal vaccine delivered via immuno-stimulating complexes induces low level of immunity against simian-HIV. Vaccine. 2006;24:6839-49 pubmed..We predict that if coadministered with additional epitopes and/or more efficacious mucosal delivery system or route, HIV/SIV-derived peptide vaccines may have potential to elicit heterologous protection. ..
- Letvin N, Mascola J, Sun Y, Gorgone D, Buzby A, Xu L, et al. Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys. Science. 2006;312:1530-3 pubmed..These immune correlates of vaccine efficacy should guide the evaluation of AIDS vaccines in humans. ..
- Johnson R, Glickman R, Yang J, Kaur A, Dion J, Mulligan M, et al. Induction of vigorous cytotoxic T-lymphocyte responses by live attenuated simian immunodeficiency virus. J Virol. 1997;71:7711-8 pubmed
- Vogel T, Horton H, Fuller D, Carter D, Vielhuber K, O Connor D, et al. Differences between T cell epitopes recognized after immunization and after infection. J Immunol. 2002;169:4511-21 pubmed..The repertoire of the immune response detected in the peripheral blood after immunization substantially differed from the immune response detected in the peripheral blood after infection. ..
- Vogel T, Reynolds M, Fuller D, Vielhuber K, Shipley T, Fuller J, et al. Multispecific vaccine-induced mucosal cytotoxic T lymphocytes reduce acute-phase viral replication but fail in long-term control of simian immunodeficiency virus SIVmac239. J Virol. 2003;77:13348-60 pubmed
- Schell J, Rose N, Bahl K, Diller K, Buonocore L, Hunter M, et al. Significant protection against high-dose simian immunodeficiency virus challenge conferred by a new prime-boost vaccine regimen. J Virol. 2011;85:5764-72 pubmed publisher..Although the immune correlates of protection are not yet clear, the heterologous VSV/SFVG prime-boost is clearly a potent vaccine regimen for inducing virus nAbs and protection against a heterogeneous viral swarm. ..
- Fuller D, Shipley T, Allen T, Fuller J, Wu M, Horton H, et al. Immunogenicity of hybrid DNA vaccines expressing hepatitis B core particles carrying human and simian immunodeficiency virus epitopes in mice and rhesus macaques. Virology. 2007;364:245-55 pubmed..These data demonstrate that immunization with hybrid HBcAg-epitope DNA vaccines is an effective strategy to increase the magnitude and breadth of HIV-specific CTL responses. ..
- Manrique M, Kozlowski P, Cobo Molinos A, Wang S, Wilson R, Montefiori D, et al. Long-term control of simian immunodeficiency virus mac251 viremia to undetectable levels in half of infected female rhesus macaques nasally vaccinated with simian immunodeficiency virus DNA/recombinant modified vaccinia virus Ankara. J Immunol. 2011;186:3581-93 pubmed publisher..Postchallenge immunological correlates of protection were systemic anti-SIV Gag + Env CD4(+)/IL-2(+), CD4(+)/IFN-?(+), and CD8(+)/TNF-?(+) T cells and vaginal anti-SIV Gag + Env CD8(+) T cell total monofunctional responses. ..
- Letvin N, Huang Y, Chakrabarti B, Xu L, Seaman M, Beaudry K, et al. Heterologous envelope immunogens contribute to AIDS vaccine protection in rhesus monkeys. J Virol. 2004;78:7490-7 pubmed
- Goulder P, Watkins D. Impact of MHC class I diversity on immune control of immunodeficiency virus replication. Nat Rev Immunol. 2008;8:619-30 pubmed publisher..Here, we review recent studies of T-cell-mediated control of HIV and SIV infection, and offer insight for the design of a successful T-cell-based HIV vaccine in the future. ..
- Suh Y, Park K, Sauermann U, Franz M, Norley S, Wilfingseder D, et al. Reduction of viral loads by multigenic DNA priming and adenovirus boosting in the SIVmac-macaque model. Vaccine. 2006;24:1811-20 pubmed..These results indicate that the multigenic DNA prime-adenovirus boost immunization may be a promising approach in developing an effective AIDS vaccine. ..
- Virnik K, Ni Y, Berkower I. Enhanced expression of HIV and SIV vaccine antigens in the structural gene region of live attenuated rubella viral vectors and their incorporation into virions. Vaccine. 2013;31:2119-25 pubmed publisher..The rubella vaccine strain readily infects rhesus macaques, and these animals will be the model of choice for testing vector growth in vivo and immunogenicity...
- Khatissian E, Monceaux V, Cumont M, Kieny M, Aubertin A, Hurtrel B. Persistence of pathogenic challenge virus in macaques protected by simian immunodeficiency virus SIVmacDeltanef. J Virol. 2001;75:1507-15 pubmed
- Rosati M, Bergamaschi C, Valentin A, Kulkarni V, Jalah R, Alicea C, et al. DNA vaccination in rhesus macaques induces potent immune responses and decreases acute and chronic viremia after SIVmac251 challenge. Proc Natl Acad Sci U S A. 2009;106:15831-6 pubmed publisher..These results demonstrate that DNA vaccination in the absence of any heterologous boost can provide protection from high viremia comparable to any other vaccine modalities tested in this macaque model. ..
- Abel K, Compton L, Rourke T, Montefiori D, Lu D, Rothaeusler K, et al. Simian-human immunodeficiency virus SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239 is independent of the route of immunization and is associated with a combination of cytotoxic T-lymphocyte and alpha interferon r. J Virol. 2003;77:3099-118 pubmed..Thus, innate as well as cellular anti-SIV immune responses appeared to contribute to the SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239. ..
- Hidajat R, Xiao P, Zhou Q, Venzon D, Summers L, Kalyanaraman V, et al. Correlation of vaccine-elicited systemic and mucosal nonneutralizing antibody activities with reduced acute viremia following intrarectal simian immunodeficiency virus SIVmac251 challenge of rhesus macaques. J Virol. 2009;83:791-801 pubmed publisher..The pattern of elevated immune responses in the I/O group is consistent with its better control of acute viremia mediated, at least in part, by ADCVI activity and transcytosis inhibition. ..
- McDermott A, O Connor D, Fuenger S, Piaskowski S, Martin S, Loffredo J, et al. Cytotoxic T-lymphocyte escape does not always explain the transient control of simian immunodeficiency virus SIVmac239 viremia in adenovirus-boosted and DNA-primed Mamu-A*01-positive rhesus macaques. J Virol. 2005;79:15556-66 pubmed..These results suggest that viral "breakthrough" in vaccinated animals and viral escape are not inextricably linked and underscore the need for additional research into the mechanisms of vaccine failure. ..
- Velu V, Kannanganat S, Ibegbu C, Chennareddi L, Villinger F, Freeman G, et al. Elevated expression levels of inhibitory receptor programmed death 1 on simian immunodeficiency virus-specific CD8 T cells during chronic infection but not after vaccination. J Virol. 2007;81:5819-28 pubmed
- Kuate S, Stahl Hennig C, ten Haaft P, Heeney J, Uberla K. Single-cycle immunodeficiency viruses provide strategies for uncoupling in vivo expression levels from viral replicative capacity and for mimicking live-attenuated SIV vaccines. Virology. 2003;313:653-62 pubmed
- Virnik K, Ni Y, Berkower I. Live attenuated rubella viral vectors stably express HIV and SIV vaccine antigens while reaching high titers. Vaccine. 2012;30:5453-8 pubmed publisher..Rubella readily infects rhesus macaques, and these animals will provide an ideal model for testing the new vectors for replication in vivo, immunogenicity, and protection against SIV or SHIV challenge...
- Rollman E, Smith M, Brooks A, Purcell D, Zuber B, Ramshaw I, et al. Killing kinetics of simian immunodeficiency virus-specific CD8+ T cells: implications for HIV vaccine strategies. J Immunol. 2007;179:4571-9 pubmed..The delayed cytolytic phenotype exhibited by standard vector-based vaccine-induced CTLs may limit the ability of T cell-based HIV vaccines to rapidly control acute infection following a pathogenic lentiviral exposure. ..
- Stahl Hennig C, Kuate S, Franz M, Suh Y, Stoiber H, Sauermann U, et al. Atraumatic oral spray immunization with replication-deficient viral vector vaccines. J Virol. 2007;81:13180-90 pubmed
- Tenner Racz K, Stahl Hennig C, Uberla K, Stoiber H, Ignatius R, Heeney J, et al. Early protection against pathogenic virus infection at a mucosal challenge site after vaccination with attenuated simian immunodeficiency virus. Proc Natl Acad Sci U S A. 2004;101:3017-22 pubmed..Therefore, during tonsillar SIV Delta nef vaccination, infection is blocked early at the entry portal, which we propose is due in part to innate functions of gamma delta T and dendritic cells. ..
- Casimiro D, Cox K, Tang A, Sykes K, Feng M, Wang F, et al. Efficacy of multivalent adenovirus-based vaccine against simian immunodeficiency virus challenge. J Virol. 2010;84:2996-3003 pubmed publisher..The implications of these results in light of the recent discouraging results of the phase IIb study of the trivalent Ad5 HIV-1 vaccine are discussed. ..
- Reynolds M, Weiler A, Piaskowski S, Kolar H, Hessell A, Weiker M, et al. Macaques vaccinated with simian immunodeficiency virus SIVmac239Delta nef delay acquisition and control replication after repeated low-dose heterologous SIV challenge. J Virol. 2010;84:9190-9 pubmed publisher..Overall, our results suggest that a well-designed HIV vaccine might both reduce the rate of acquisition and control viral replication. ..
- Hansen S, Sacha J, Hughes C, Ford J, Burwitz B, Scholz I, et al. Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science. 2013;340:1237874 pubmed publisher..5, Rh157.4, and Rh157.6 (human CMV UL128, UL130, and UL131) genes. Thus, CMV vectors can be genetically programmed to achieve distinct patterns of CD8(+) T cell epitope recognition...
- Hessell A, Poignard P, Hunter M, Hangartner L, Tehrani D, Bleeker W, et al. Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques. Nat Med. 2009;15:951-4 pubmed publisher..Overall, the results imply that lower amounts of antibody than previously considered protective may provide benefit in the context of typical human exposure to HIV-1. ..
- Liu J, O Brien K, Lynch D, Simmons N, La Porte A, Riggs A, et al. Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys. Nature. 2009;457:87-91 pubmed publisher..These findings have important implications for the development of next-generation T-cell-based vaccine candidates for HIV-1. ..
- Rosati M, Valentin A, Jalah R, Patel V, von Gegerfelt A, Bergamaschi C, et al. Increased immune responses in rhesus macaques by DNA vaccination combined with electroporation. Vaccine. 2008;26:5223-9 pubmed publisher..These results indicate that improved gene delivery and expression by electroporation dramatically increases immunogenicity of DNA vaccines. Electroporation is thus an important method to improve the effectiveness of DNA vaccination. ..
- Keele B, Li H, Learn G, Hraber P, Giorgi E, Grayson T, et al. Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J Exp Med. 2009;206:1117-34 pubmed publisher..These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV-macaque mucosal infection model for HIV-1 vaccine and microbicide research. ..
- Hansen S, Ford J, Lewis M, Ventura A, Hughes C, Coyne Johnson L, et al. Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature. 2011;473:523-7 pubmed publisher..Thus, persistent vectors such as CMV and their associated T(EM) responses might significantly contribute to an efficacious HIV/AIDS vaccine. ..
- Lai L, Kwa S, Kozlowski P, Montefiori D, Ferrari G, Johnson W, et al. Prevention of infection by a granulocyte-macrophage colony-stimulating factor co-expressing DNA/modified vaccinia Ankara simian immunodeficiency virus vaccine. J Infect Dis. 2011;204:164-73 pubmed publisher..The prevention of infection showed a strong correlation with the avidity of the elicited Env-specific antibody for the Env of the SIVsmE660 challenge virus (r = 0.9; P < .0001). ..
- Stahl Hennig C, Dittmer U, Nisslein T, Petry H, Jurkiewicz E, Fuchs D, et al. Rapid development of vaccine protection in macaques by live-attenuated simian immunodeficiency virus. J Gen Virol. 1996;77 ( Pt 12):2969-81 pubmed..Nevertheless, such a vaccine raises severe safety concerns because of its potential to revert to virulence. ..
- Johnston R, Johnson P, Connell M, Montefiori D, West A, Collier M, et al. Vaccination of macaques with SIV immunogens delivered by Venezuelan equine encephalitis virus replicon particle vectors followed by a mucosal challenge with SIVsmE660. Vaccine. 2005;23:4969-79 pubmed..Significantly elevated levels of CD4+ T cells were observed post-challenge. A strong correlation was noted between a net increase in CD4+ T cell count and lowered virus load at set point. ..
- Hofmann Lehmann R, Vlasak J, Williams A, Chenine A, McClure H, Anderson D, et al. Live attenuated, nef-deleted SIV is pathogenic in most adult macaques after prolonged observation. AIDS. 2003;17:157-66 pubmed..Thus, mass vaccination of humans with similarly constructed live attenuated HIV vaccines, recently suggested for countries with high HIV-1 transmission rates, seems contraindicated. ..
- Das A, Klaver B, Centlivre M, Harwig A, Ooms M, Page M, et al. Optimization of the doxycycline-dependent simian immunodeficiency virus through in vitro evolution. Retrovirology. 2008;5:44 pubmed publisher..The dox-dependent SIV-rtTA variant was optimized by viral evolution, yielding variants that can be used to test the conditionally live virus vaccine approach and as a tool in SIV biology studies and vaccine research. ..
- Wodarz D. Immunity and protection by live attenuated HIV/SIV vaccines. Virology. 2008;378:299-305 pubmed publisher..According to these arguments, an inverse correlation between the level of attenuation and the level of protection is expected, and this has indeed been observed in experimental data. ..
- Berry N, Stebbings R, Ferguson D, Ham C, Alden J, Brown S, et al. Resistance to superinfection by a vigorously replicating, uncloned stock of simian immunodeficiency virus (SIVmac251) stimulates replication of a live attenuated virus vaccine (SIVmacC8). J Gen Virol. 2008;89:2240-51 pubmed publisher..The role of innate and intrinsic anti-retroviral immunity in the protection conferred by live attenuated SIV vaccines warrants careful study. ..
- Stebbings R, Almond N, Stott E, Berry N, Wade Evans A, Hull R, et al. Mechanisms of protection induced by attenuated simian immunodeficiency virus. Virology. 2002;296:338-53 pubmed..These data do not support the hypothesis that protection conferred by live attenuated SIV is mediated by the induction of vigorous T-cell responses upon rechallenge. ..