Recombinant Modified Vaccinia Virus Ankara Expressing the Surface gp120 of Simian Immunodeficiency Virus (SIV) Primes for a Rapid Neutralizing Antibody Response to SIV Infection in Macaques

Ourmanov, Ilnour; Bilska, Miroslawa; Hirsch, Vanessa M.; Montefiori, David C.

doi:10.1128/jvi.74.6.2960-2965.2000

Cited by 53 publications

(47 citation statements)

References 50 publications

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“…SIVsmE660 infection elicited anamnestic SIVsmH4-specific NAb responses, indicating cross-reactive memory CD4 T cells and B cells, but the antibodies did not limit SIVsmE660 replication. The SIVsmH4-vaccine-specific NAb response is consistent with previous studies demonstrating a dichotomy in the neutralization phenotypes of SIVsmH4 and SIVsmE660 and highly strain-specific NAbs during the first 6 weeks of infection (36). (Similarly, current HIV vaccine candidates also do not elicit cross-reactive NAbs against primary isolates, but likely will elicit cross-reactive CD4 Th responses.)…”

Section: Discussionsupporting

confidence: 87%

Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein

Staprans

Barry

Silvestri

et al. 2004

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

130

113

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Given the dual role of CD4 T cells as both immune effectors and targets for HIV infection, the balance of CD4 versus CD8 T cellmediated responses induced by candidate AIDS vaccines may be critical in determining postvaccination infection outcomes. An attenuated recombinant varicella-zoster virus vaccine expressing the simian immunodeficiency virus (SIV) envelope (Env) elicited nonneutralizing Env-binding antibodies and little if any cytotoxic T lymphocyte responses in rhesus macaques (Macaca mulatta). After challenge with SIV, Env vaccinees manifested increased levels of SIV replication, more rapid CD4 depletion, and accelerated progression to AIDS compared with controls. Enhanced SIV replication correlated with increased CD4 T cell proliferation soon after SIV challenge, apparently the result of an anamnestic response to SIV antigens. Thus activation of virusspecific CD4 T cells at the time of exposure to a CD4 T cell-tropic lentivirus, in the absence of an effective CD8 response, may enhance virus replication and disease. 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.

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Section: Discussionsupporting

confidence: 87%

Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein

Staprans

Barry

Silvestri

et al. 2004

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

130

113

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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: 53%

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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“…[75][76][77][78] One of these studies, by Lim and colleagues, observed significant differences in the ability of different TRIM5a alleles present in these macaques to inhibit infection by SIVmac239, a viral strain commonly used to infect rhesus macaques to induce an AIDS-like disease in studies of AIDS pathogenesis and vaccine strategies. [79][80][81] Critically, not only did intraspecies allelic differences affect restriction of SIVmac239 in single cycle infectivity assays, these differences also conferred altered susceptibility to critical aspects of AIDS-like disease progression, including peak and set-point plasma RNA levels, CD4 T cell depletion, and survival. 76 Another similar study by Kirmaier et al found that many of the same rhTRIM5a alleles examined in the Lim study also differentially affected the replication of another commonly used laboratory strain, SIVsmE543-3.…”

Section: The Emerging Relationship Between Capsid Recognition Domainsmentioning

confidence: 99%

Recent Insights into the Mechanism and Consequences of TRIM5α Retroviral Restriction

Sastri

Campbell

2011

AIDS Research and Human Retroviruses

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The cellular factor TRIM5a inhibits infection by numerous retroviruses in a species-specific manner. The TRIM5a protein from rhesus macaques (rhTRIM5a) restricts infection by HIV-1 while human TRIM5a (huTRIM5a) restricts infection by murine leukemia virus (MLV). In owl monkeys a related protein TRIM-Cyp restricts HIV-1 infection. Several models have been proposed for retroviral restriction by TRIM5 proteins (TRIM5a and TRIMCyp). These models collectively suggest that TRIM5 proteins mediate restriction by directly binding to specific determinants in the viral capsid. Through their ability to self-associate TRIM5 proteins compartmentalize the viral capsid core and mediate its abortive disassembly via a poorly understood mechanism that is sensitive to proteasome inhibitors. In this review, we discuss TRIM5-mediated restriction in detail. We also discuss how polymorphisms within human and rhesus macaque populations have been demonstrated to affect disease progression of immunodeficiency viruses in these species.

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Recombinant Modified Vaccinia Virus Ankara Expressing the Surface gp120 of Simian Immunodeficiency Virus (SIV) Primes for a Rapid Neutralizing Antibody Response to SIV Infection in Macaques

Cited by 53 publications

References 50 publications

Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein

Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein

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

Recent Insights into the Mechanism and Consequences of TRIM5α Retroviral Restriction

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