Critical Role for Env as well as Gag-Pol in Control of a Simian-Human Immunodeficiency Virus 89.6P Challenge by a DNA Prime/Recombinant Modified Vaccinia Virus Ankara Vaccine

Amara, Rama Rao; Smith, James M.; Staprans, Silvija I.; Montefiori, David C.; Villinger, François; Altman, John D.; O’Neil, Shawn P.; Kozyr, Natalia; Xu, Yixin; Wyatt, Linda S.; Earl, Patricia L.; Herndon, James G.; McNicholl, Janet M.; McClure, Harold M.; Moss, Bernard; Robinson, Harriet L.

doi:10.1128/jvi.76.12.6138-6146.2002

Cited by 146 publications

(102 citation statements)

References 24 publications

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“…4f). Although we were not able to consistently induce broad responses to other SHIV proteins by these vaccines, our results lend support to the concept that this should be advantageous (2). It would ultimately also be insightful to immunize macaques against a B subtype SHIV and then challenge with a subtype AE SHIV; however, such virus constructs are not available at present.…”

Section: Discussionmentioning

confidence: 49%

Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

Rose

Batten

Smith

et al. 2007

J Virol

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Vaccination against AIDS is hampered by great diversity between human immunodeficiency virus (HIV) strains. Heterologous B-subtype-based simian-human immunodeficiency virus (SHIV) DNA prime and poxvirus boost vaccine regimens can induce partial, T-cell-mediated, protective immunity in macaques. We analyzed a set of DNA, recombinant fowlpox viruses (FPV), and vaccinia viruses (VV) expressing subtype AE HIV type 1 (HIV-1) Tat, Rev, and Env proteins and SIV Gag/Pol in 30 pigtail macaques. SIV Gag-specific CD4 and CD8 T-cell responses were induced by sequential DNA/FPV vaccination, although lower FPV doses, VV/FPV vaccination, and DNA vaccines alone were not as consistently immunogenic. The SHIV AE DNA prime, FPV boost regimens were significantly less immunogenic than comparable B-subtype SHIV vaccination. Peak viral load was modestly (0.4 log 10 copies/ml) lower among the AE subtype SHIV-immunized animals compared to controls following the virulent B subtype SHIV challenge. Protection from persistent high levels of viremia and CD4 T-cell depletion was less in AE subtype compared to B subtype SHIV-vaccinated macaques. Gag was highly immunodominant over the other AE subtype SHIV vaccine proteins after vaccination, and this immunodominance was exacerbated after challenge. Interestingly, the lower level of priming of immune responses did not blunt postchallenge Gag-specific recall responses, despite more modest protection. These studies suggest priming of T-cell immunity to prevent AIDS in humans is possible, but differences in the immunogenicity of various subtype vaccines and broad cross-subtype protection are substantial hurdles.

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Section: Discussionmentioning

confidence: 49%

Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

Rose

Batten

Smith

et al. 2007

J Virol

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“…Neutralization titers were negative on the day of challenge and 4 wk after challenge, became detectable by wk 8, and increased with time in some of the animals. The similar timing of the development of this response in group 1, 2, and 3 vaccinated animals compared with group 4 and historic controls excludes priming of neutralizing Abs by the vaccination regimen (61)(62)(63)(64). After wk 45, titers of neutralizing Ab increased in only a few animals of groups 1, 3, and 4.…”

Section: Protection From Shiv Infection And/or Simian Aids After Mucomentioning

confidence: 92%

Control of Simian/Human Immunodeficiency Virus Viremia and Disease Progression after IL-2-Augmented DNA-Modified Vaccinia Virus Ankara Nasal Vaccination in Nonhuman Primates

Bertley

Kozlowski

Wang

et al. 2004

The Journal of Immunology

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A successful HIV vaccine may need to stimulate antiviral immunity in mucosal and systemic immune compartments, because HIV transmission occurs predominantly at mucosal sites. We report here the results of a combined DNA-modified vaccinia virus Ankara (MVA) vaccine approach that stimulated simian/human immunodeficiency virus (SHIV)-specific immune responses by vaccination at the nasal mucosa. Fifteen male rhesus macaques, divided into three groups, received three nasal vaccinations on day 1, wk 9, and wk 25 with a SHIV DNA plasmid producing noninfectious viral particles (group 1), or SHIV DNA plus IL-2/Ig DNA (group 2), or SHIV DNA plus IL-12 DNA (group 3). On wk 33, all macaques were boosted with rMVA expressing SIV Gag-Pol and HIV Env 89.6P, administered nasally. Humoral responses were evaluated by measuring SHIV-specific IgG and neutralizing Abs in plasma, and SHIV-specific IgA in rectal secretions. Cellular responses were monitored by evaluating blood-derived virus-specific IFN-γ-secreting cells and TNF-α-expressing CD8+ T cells, and blood- and rectally derived p11C tetramer-positive T cells. Many of the vaccinated animals developed both mucosal and systemic humoral and cell-mediated anti-SHIV immune responses, although the responses were not homogenous among animals in the different groups. After rectal challenge of vaccinated and naive animals with SHIV89.6P, all animals became infected. However a subset, including all group 2 animals, were protected from CD4+ T cell loss and AIDS development. Taken together, these data indicate that nasal vaccination with SHIV-DNA plus IL-2/Ig DNA and rMVA can provide significant protection from disease progression.

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“…This view stems from demonstrations that the passive transfer of broadly cross-reactive, neutralizing antienvelope antibodies affords sterilizing protection in nonhuman primate models for HIV infection (1)(2)(3). Moreover, certain vaccine strategies are more effective in suppressing infection in nonhuman primate models when viral envelope is included in the vaccine (4,5). Recent evidence indicates that anti-envelope antibody-dependent cellular cytotoxicity activity correlates with protection against HIV challenge (6).…”

mentioning

confidence: 99%

Antibodies to CD4-induced sites in HIV gp120 correlate with the control of SHIV challenge in macaques vaccinated with subunit immunogens

DeVico

Fouts

Lewis

et al. 2007

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

109

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Epitopes located in and around the coreceptor binding site of HIV-1 envelope glycoprotein (gp120) exhibit enhanced exposure after attachment to the CD4 receptor and comprise some of the most conserved and functionally important residues on the viral envelope. Therefore, antibody responses to these epitopes [designated as CD4-induced (CD4i)] should be highly cross-reactive and potentially useful for HIV vaccine development. To address this question, rhesus macaques were vaccinated with subunit immunogens designed to raise humoral responses against CD4i epitopes and challenged rectally with SHIV 162P3, which encodes a heterologous envelope versus the immunogen. We found that animals vaccinated with a rhesus full-length single-chain (rhFLSC) complex exhibited significantly accelerated clearance of plasma viremia and an absence of long-term tissue viremia compared with unvaccinated control animals. Such control of infection correlated with stronger responses to CD4i epitopes in the rhFLSC-vaccinated animals, compared with macaques immunized with gp120, crosslinked gp120 -CD4 complexes, or soluble CD4 alone. These responses were strongly boosted in the rhFLSC-vaccinated animals by SHIV 162P3 infection. The control of infection was not associated with anti-CD4 responses, overall anti-gp120-binding titers, or neutralizing activity measured in conventional assays. Vaccine-naive animals also developed anti-CD4i epitope responses after simian/ human immunodeficiency virus (SHIV) challenge, which appeared later than the overall anti-gp120 responses and in concert with the decline of viremia to a low set point. Collectively, these data suggest that antibodies to CD4i epitopes may play a role in controlling SHIV infection and provide insights for HIV vaccine development.vaccine ͉ infection ͉ immunity

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Critical Role for Env as well as Gag-Pol in Control of a Simian-Human Immunodeficiency Virus 89.6P Challenge by a DNA Prime/Recombinant Modified Vaccinia Virus Ankara Vaccine

Cited by 146 publications

References 24 publications

Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

Control of Simian/Human Immunodeficiency Virus Viremia and Disease Progression after IL-2-Augmented DNA-Modified Vaccinia Virus Ankara Nasal Vaccination in Nonhuman Primates

Antibodies to CD4-induced sites in HIV gp120 correlate with the control of SHIV challenge in macaques vaccinated with subunit immunogens

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