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At least 55 records · Page 3Linked to original sources
PubMed2003

Magnitude and diversity of cytotoxic-T-lymphocyte responses elicited by multiepitope DNA vaccination in rhesus monkeys.

In an effort to develop an AIDS vaccine that elicits high-frequency cytotoxic-T-lymphocyte (CTL) responses with specificity for a diversity of viral epitopes, we explored two prototype multiepitope plasmid DNA vaccines in the simian-human immunodeficiency virus/rhesus monkey model to determine their efficiency in priming for such immune responses. While a simple multiepitope vaccine construct demonstrated limited immunogenicity in monkeys, this same multiepitope genetic sequence inserted into an immunogenic simian immunodeficiency virus gag DNA vaccine elicited high-frequency CTL responses specific for all of the epitopes included in the vaccine. Both multiepitope vaccine prototypes primed for robust epitope-specific CTL responses that developed following boosting with recombinant modified vaccinia virus Ankara vaccines expressing complete viral proteins. The natural hierarchy of immunodominance for these epitopes was clearly evident in the boosted monkeys. These studies suggest that multiepitope plasmid DNA vaccine-based prime-boost regimens can efficiently prime for CTL responses of increased breadth and magnitude, although they do not overcome predicted hierarchies of immunodominance.

AIDS Vaccines↗
PubMed2004

SIVmac Gag p27 capsid protein gene expression in potato.

A cDNA encoding the Simian immunodeficiency virus type (SIV(mac)) Gag capsid protein was introduced into Solanum tuberosum cells by Agrobacterium tumefaciens-mediated transformation methods. The gag gene was detected in the genomic DNA of transformed leaf tissues by PCR DNA amplification. Immunoblot analysis of transformed potato plant extracts with anti-Gag monoclonal antibody showed that biologically active Gag protein was synthesized in transformed tuber tissues. Based on ELISA results, recombinant Gag protein made up 0.006-0.014% of total soluble tuber protein. The synthesis of SIV Gag in transformed potato tubers opens the way for development of Gag-based edible plant vaccines for protection against SIV and potentially HIV-1 infection.

AIDS Vaccines↗
PubMed1995

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

A vaccine against AIDS will probably have to protect against challenge both by viable virus-infected cells and by cell-free virus. Eight cynomolgus macaques infected with attenuated simian immunodeficiency virus (SIV) were challenged (four each) with cell-free and cell-associated SIV. All were protected, whereas eight controls were all infected after challenge. These findings show that live-attenuated vaccine can confer protection against SIV in macaques. Extrapolation to human beings will require extensive evaluation of the safety of attenuated retroviruses. Alternatively, the mechanism of this potent protection must be understood and reproduced by less hazardous means.

AIDS Vaccines↗
PubMed2004

An SHIV DNA/MVA rectal vaccination in macaques provides systemic and mucosal virus-specific responses and protection against AIDS.

We explored the use of a simian-human immunodeficiency virus (SHIV) DNA vaccine as an effective mucosal priming agent to stimulate a protective immune response for AIDS prevention. Rhesus macaques were vaccinated rectally with a DNA construct producing replication-defective SHIV particles, and boosted with either the same DNA construct or recombinant modified vaccinia virus Ankara (MVA) expressing SIV Gag, SIV Pol, and HIV Env (MVA-SHIV). Virus-specific mucosal and systemic humoral and cell-mediated immune responses could be stimulated by this approach but were present inconsistently among the vaccinated animals. Rectal vaccination with either SHIV DNA alone or SHIV DNA followed by MVA-SHIV induced SIV Gag/Pol- or HIV gp120-specific IgA in rectal secretions of four of seven animals. However, the gp120-specific rectal IgA antibody responses were not durable and had become undetectable in all but one animal shortly before rectal challenge with pathogenic SHIV 89.6P. Only the macaques primed with SHIV DNA and boosted with MVA-SHIV demonstrated SHIV-specific IgG in plasma. In addition, these animals developed more consistent antiviral cell-mediated responses and had better preservation of CD4 T cells following challenge with SHIV 89.6P. Our study demonstrates the utility of a rectal DNA/MVA vaccination protocol for the induction of diverse responses in different immunological compartments. In addition, the immunity achieved with this mucosal vaccination regimen is sufficient to delay progression to AIDS.

AIDS Vaccines↗
PubMed2002

Prior vaccination increases the epitopic breadth of the cytotoxic T-lymphocyte response that evolves in rhesus monkeys following a simian-human immunodeficiency virus infection.

Although recent evidence has confirmed the importance of cytotoxic T-lymphocyte (CTL) responses in controlling human immunodeficiency virus type 1 and simian immunodeficiency virus replication, the relevance of the epitopic breadth of those CTL responses remains unexplored. In the present study, we sought to determine whether vaccination can expand CTL populations which recognize a repertoire of viral epitopes that is greater than is typically generated in the course of a viral infection. We demonstrate that potent secondary CTL responses to subdominant epitopes are rapidly generated following a pathogenic simian-human immunodeficiency virus challenge of rhesus monkeys vaccinated with plasmid DNA or recombinant modified vaccinia virus Ankara vaccines. These data indicate that prior vaccination can increase the breadth of the CTL response that evolves after an AIDS virus infection.

AIDS Vaccines↗
PubMedDate not supplied

HIV vaccine development in the nonhuman primate model of AIDS.

Development of a prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine is a leading priority in biomedical research. Much of this work has been done with the nonhuman primate model of AIDS. In a historical context, vaccine studies, which use this model, are summarized and discussed.

AIDS Vaccines↗
PubMed1999

Live attenuated AIDS viruses as vaccines: promise or peril?

Live attenuated viruses can provide vaccine protection against various viral illnesses. A number of live attenuated strains of the simian immunodeficiency virus (SIV) or related lentiviruses have been evaluated in primate models as vaccine candidates against AIDS. Impressive efficacy was observed for some viruses, most notably SIV strains with deletions in the nef-gene. Sterilizing immunity was seen against homologous and heterologous virus challenge, against cell-free and cell-associated challenge, against intravenous and mucosal challenge, and against challenge as early as 3 weeks and as late as 2.25 years after just one immunization. However, these promising efficacy results are overshadowed by safety problems, such as reversion of the vaccine strain to a pathogenic virus encoding full-length nef or residual virulence of multiply deleted vaccine strains. Strategies aimed at decreasing the replicative capacity of nef-deleted vaccine strains to increase the safety profile have significantly curtailed vaccine efficacy. Nevertheless, studies of live attenuated vaccine strains should proceed and should focus on determining the correlates of vaccine protection and the molecular determinants for virulence and attenuation.

AIDS Vaccines↗
PubMed2000

DNA priming and recombinant pox virus boosters for an AIDS vaccine.

Eight different protocols for immunization have been compared for the ability to raise protection against immunodeficiency virus challenges in rhesus macaques. The most promising containment of challenge infections was achieved by intradermal DNA priming followed by recombinant fowl pox virus booster immunizations. This containment did not require neutralizing antibody and was active for a series of challenges ending with a highly virulent virus with a primary isolate envelope heterologous to the immunizing strain.

AIDS Vaccines↗
PubMed2005

Protection by dendritic cells-based HIV synthetic peptide cocktail vaccine: preclinical studies in the SHIV-rhesus model.

Vaccine development efforts against HIV-1 have been hindered because of the high mutation rate of the virus, and limitations for direct testing of HIV antigens in animal models to discern the nature of protective immunity. We developed a multivalent vaccine comprised of highly conserved HIV envelope peptide cocktail focused on priming antigen-specific helper T cell and CTL responses. Here we report protection of rhesus macaques against pathogenic SHIV(89.6P) challenge through priming cell-mediated immunity by prophylactic vaccination with the peptide-cocktail delivered by dendritic cells. Compared to monkeys mock-vaccinated or immunized with the peptide cocktail using IFA, vaccination with peptide cocktail-pulsed DC showed significant protection from AIDS-associated mortality and reduction in plasma viremia to undetectable levels.

AIDS Vaccines↗
PubMed2002

Preclinical AIDS vaccine research: survey of SIV, SHIV, and HIV challenge studies in vaccinated nonhuman primates.

This current supplementary and systematic survey of 237 preclinical AIDS vaccine challenge/protection studies in nonhuman primates enumerates and broadly describes the recent status of different vaccine strategies in macaque and chimpanzee experimental models. Published studies since the previous survey were compiled and categorized by their vaccine types, challenge parameters, and challenge results. These models have supportively verified that some prophylactic vaccine approaches, though rarely preventing infection (which is observed in these models with some passively administered antibody-based vaccines), can control to some degree primate lentivirus replication and disease development, and this is encouraging because it places more potentially effective immunogens on the precipice for early clinical studies. Many of these promising approaches may benefit from more testing in mucosal challenge models, and resources will be needed to follow more of these partially protected vaccinees for longer periods.

AIDS Vaccines↗
PubMed1997

Expression of gamma interferon by simian immunodeficiency virus increases attenuation and reduces postchallenge virus load in vaccinated rhesus macaques.

Simian immunodeficiency virus (SIV) infection of macaques is a model for human immunodeficiency virus (HIV) infection. We have previously reported the construction and characterization of an SIV vector with a deletion in the nef gene (SIV(delta nef)) and expressing gamma interferon (SIV(HyIFN)) (L. Giavedoni and T. Yilma, J. Virol. 70:2247-2251, 1996). We now show that rhesus macaques vaccinated with SIV(HyIFN) have a lower viral load than a group similarly immunized with SIV(delta nef). Viral loads remained low in the SIV(HyIFN)-vaccinated group even though SIV expressing gamma interferon could not be isolated after 6 weeks postimmunization in these animals. All immunized and two naive control macaques became infected when challenged with virulent SIV(mac251), at 25 weeks postvaccination. In contrast to the two naive controls that died by 12 and 18 weeks postchallenge, all vaccinated animals remained healthy for more than 32 weeks. In addition, postchallenge cell-associated virus load was significantly lower in SIV(HyIFN)-immunized animals than in the group vaccinated with SIV(delta nef). These findings indicate that cytokine-expressing viruses can provide a novel approach for development of safe and efficacious live attenuated vaccines for AIDS.

Animals↗
PubMed1999

Passively administered neutralizing serum that protected macaques against infection with parenterally inoculated pathogenic simian-human immunodeficiency virus failed to protect against mucosally inoculated virus.

Macaques inoculated orally, vaginally, or parenterally with SHIV(KU-1) develop severe systemic infection, acute loss of CD4+ T cells, and AIDS. We showed in a previous report that passive immunization with neutralizing serum protected macaques against infection with parenterally inoculated pathogenic SHIV given 24 hr later. In the study reported here we asked whether the identical passive immunization protocol would protect macaques against infection with pathogenic SHIV following oral inoculation of the virus. Ten pigtail macaques were inoculated orally with one animal infectious dose of SHIV(KU-1). Four of the 10 had been given pooled anti-SHIV plasma (15 ml/kg) 24 hr earlier, 4 others were given the same dose of anti-SHIV plasma 2 hr after virus challenge, and the 2 remaining animals were used as controls. The neutralizing antibodies failed to protect macaques against infection after mucosal challenge with SHIV(KU-1).

AIDS Vaccines↗