Reduction of Simian-Human Immunodeficiency Virus 89.6P Viremia in Rhesus Monkeys by Recombinant Modified Vaccinia Virus Ankara Vaccination

Barouch, Dan H.; Santra, Sampa; Kuroda, Marcelo J.; Schmitz, Jörn E.; Plishka, Ronald J.; Buckler-White, Alicia; Gaitan, Alicia; Zin, Rebekah; Nam, Jae‐Hwan; Wyatt, Linda S.; Lifton, Michelle A.; Nickerson, Christine E.; Moss, Bernard; Montefiori, David C.; Hirsch, Vanessa M.; Letvin, Norman L.

doi:10.1128/jvi.75.11.5151-5158.2001

Cited by 173 publications

(118 citation statements)

References 44 publications

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“…Peak responses with recombinant pox-virus vectors have been lower, but can increase dramatically after one or two subunit protein boosts [37][38][39][40][41][42], suggesting effective B-cell priming by the vectored immunogen. Similar secondary neutralizing antibody responses are observed post-AIDS virus infection in macaques that are previously immunized with recombinant Env-containing DNA and viral vectors [43][44][45][46][47][48][49]. Furthermore, a recent study in rabbits showed that priming with a recombinant vector followed by boosting with subunit Env protein can be superior to multiple inoculations with Env protein alone [50].…”

Section: Hiv-1 Immunogenssupporting

confidence: 50%

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Haynes¹,

Montefiori²

2006

Expert Review of Vaccines

104

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Neutralizing antibody induction is a key feature of many effective vaccines and is the only immune response that has proven to be capable of completely blocking AIDS virus infection in animal models. Unfortunately, the extensive genetic variability and complex immune-evasion strategies of HIV-1 have thwarted all attempts to date at eliciting an effective neutralizing antibody response with candidate HIV-1 vaccine immunogens. Recent advances in our understanding of how these evasion strategies operate, coupled with growing progress in unravelling the structure and immunobiology of the viral envelope glycoproteins, are contributing to novel immunogen designs to overcome the many barriers to inducing protective antibodies against HIV-1. Keywordsantiretroviral therapy; HIV-1; host cell fusion; immunogen; neutralizing antibody induction Development of a safe, practical and effective HIV-1 vaccine is one of the highest priorities of the global scientific community [1,2]. Although antiretroviral therapy (ART) has dramatically prolonged the lives of HIV-1 infected patients, ART is not yet routinely available in developing countries, and the global rate of spread of HIV-1 continues unabated. If no effective AIDS vaccine is developed by 2010, the number of people infected world-wide with HIV-1 could exceed 60 million [3].In spite of more than 20 years of research, the types of immune responses needed to protect an immunized individual from HIV-1 infection are not known. Its is known that CD8 + cytotoxic T-cell responses can control HIV-1 replication to varying degrees in acute HIV-1 infection (AHI) [4,5], and when induced by immunogens, can control viral set point after simian immunodeficiancy virus (SIV) or simian HIV (SHIV) challenges in non-human primates [4]. Strong proliferative CD4 + T-cell responses to HIV-1 proteins have been demonstrated to correlate well with immune control of HIV-1 viral load [5]. Therefore, it is highly desirable for an HIV-1 vaccine co induce robust CD4 + and CD8 + T-cell responses in order to control virus replication and reduce the likelihood of subsequent transmission [4][5][6][7]. The potential for complete ('sterilizing') immunity from HIV-1 infection may depend on the presence of pre-existing neutralizing antibodies. We know that neutralizing antibodies can prevent the acquisition of AIDS virus infection after intravenous, vaginal, rectal and oral virus challenge in nonhuman primates [8][9][10][11][12]. This level of protection is highly attractive for a vaccine against a virus, such as HIV-1, which integrates genetically and forms latent viral reservoirs soon after infection. However, the diversity of transmitted HIV-1 genetic variants and the relative resistance of the majority of HIV-1 primary isolates to most types of inducible neutralizing antibodies have posed major hurdles to current vaccine efforts. Furthermore, the few rare broadly reactive neutralizing monoclonal antibodies (mAbs) that have been isolated from HIV-1 infected patients represent species of antibodies that...

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Section: Hiv-1 Immunogenssupporting

confidence: 50%

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Haynes¹,

Montefiori²

2006

Expert Review of Vaccines

104

View full text Add to dashboard Cite

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“…A competition of the two Gag derived epitopes with the immunodominant V3 epitope was not observed. These results strongly support recent findings by others demonstrating the feasibility of multiepitope DNA vaccines to elicit broad CTL responses against multiple HI-viral epitopes [41,42]. This is of particular interest in the light of previous vaccination studies in non-human primates demonstrating that single viral epitope-specific CTL responses may not be sufficient to block infection with pathogenic SIV [43,44].…”

Section: Discussionsupporting

confidence: 89%

Influence of polypeptide size and intracellular sorting on the induction of epitope-specific CTL responses by DNA vaccines in a mouse model

Wild

Bojak

Deml

et al. 2004

Vaccine

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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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Reduction of Simian-Human Immunodeficiency Virus 89.6P Viremia in Rhesus Monkeys by Recombinant Modified Vaccinia Virus Ankara Vaccination

Cited by 173 publications

References 44 publications

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Influence of polypeptide size and intracellular sorting on the induction of epitope-specific CTL responses by DNA vaccines in a mouse model

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

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