Association between Cellular Immune Activation, Target Cell Frequency, and Risk of Human Immunodeficiency Virus Type 1 Superinfection

Blish, Catherine A.; Oc, Dogan; Jaoko, Walter; McClelland, R. Scott; Mandaliya, Kishor; K, Odem-Davis; Ba, Richardson; Overbaugh, Julie

doi:10.1128/jvi.00187-14

Cited by 4 publications

(4 citation statements)

References 45 publications

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“…Indeed, the efficiency of horizontal and vertical SIV transmission in NHP hosts in the absence of vaccination is linked to the availability of susceptible target cells in the mucosa (41)(42)(43). Furthermore, there is strong evidence that genital inflammation reduces the stringency of HIV-1 transmission (25,44,45) and increased target cell availability increases the risk of HIV-1 superinfection (46).…”

Section: Discussionmentioning

confidence: 99%

Breakthrough of SIV strain smE660 challenge in SIV strain mac239-vaccinated rhesus macaques despite potent autologous neutralizing antibody responses

Burton

Kilgore

Smith

et al. 2015

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

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Although the correlates of immunological protection from human immunodeficiency virus or simian immunodeficiency virus infection remain incompletely understood, it is generally believed that medium to high titers of serum neutralizing antibodies (nAbs) against the challenge virus will prevent infection. This paradigm is based on a series of studies in which passive transfer of HIV-specific nAbs protected rhesus macaques (RMs) from subsequent mucosal challenge with a chimeric human/simian immunodeficiency virus. However, it is unknown whether nAb titers define protection in the setting of active immunization. Here we determined serum nAb titers against breakthrough transmitted/founder (T/F) SIVsmE660-derived envelope glycoprotein (Env) variants from 14 RMs immunized with SIVmac239-based DNA-prime/modified vaccinia virus Ankara-boost vaccine regimens that included GM-CSF or CD40L adjuvants and conferred significant but incomplete protection against repeated low-dose intrarectal challenge. A single Env variant established infection in all RMs except one, with no identifiable genetic signature associated with vaccination breakthrough compared with T/F Envs from four unvaccinated monkeys. Breakthrough T/F Env pseudoviruses were potently neutralized in vitro by heterologous pooled serum from chronically SIVsmE660-infected monkeys at IC50 titers exceeding 1:1,000,000. Remarkably, the T/F Env pseudoviruses from 13 of 14 monkeys were also susceptible to neutralization by autologous prechallenge serum at in vitro IC50 titers ranging from 1:742–1:10,832. These titers were similar to those observed in vaccinated RMs that remained uninfected. These data suggest that the relationship between serum nAb titers and protection from mucosal SIV challenge in the setting of active immunization is more complex than previously recognized, warranting further studies into the balance between immune activation, target cell availability, and protective antibody responses.

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Section: Discussionmentioning

confidence: 99%

Breakthrough of SIV strain smE660 challenge in SIV strain mac239-vaccinated rhesus macaques despite potent autologous neutralizing antibody responses

Burton

Kilgore

Smith

et al. 2015

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

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“… 105–111 This relatively unimpressive level of protection by live attenuated SIV against challenge by a heterologous AIDS virus strain is perhaps analogous to the inability of human infection with wild-type strains of HIV-1 to routinely protect against superinfection by different strains of HIV-1 (refs. 112–116 ).…”

Section: Vaccine Trials In Monkeysmentioning

confidence: 99%

Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies

Fuchs

Desrosiers

2016

Molecular Therapy - Methods & Clinical Development

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Attempts to elicit antibodies with potent neutralizing activity against a broad range of human immunodeficiency virus (HIV) isolates have so far proven unsuccessful. Long-term delivery of monoclonal antibodies (mAbs) with such activity is a creative alternative that circumvents the need for an immune response and has the potential for creating a long-lasting sterilizing barrier against HIV. This approach is made possible by an incredible array of potent broadly neutralizing antibodies (bnAbs) that have been identified over the last several years. Recombinant adeno-associated virus (rAAV) vectors are ideally suited for long-term delivery for a variety of reasons. The only products made from rAAV are derived from the transgenes that are put into it; as long as those products are not viewed as foreign, expression from muscle tissue may continue for decades. Thus, use of rAAV to achieve long-term delivery of anti-HIV mAbs with potent neutralizing activity against a broad range of HIV-1 isolates is emerging as a promising concept for the prevention or treatment of HIV-1 infection in humans. Experiments in mice and monkeys that have demonstrated protective efficacy against AIDS virus infection have raised hopes for the promise of this approach. However, all published experiments in monkeys have encountered unwanted immune responses to the AAV-delivered antibody, and these immune responses appear to limit the levels of delivered antibody that can be achieved. In this review, we highlight the promise of rAAV-mediated antibody delivery for the prevention or treatment of HIV infection in humans, but we also discuss the obstacles that will need to be understood and solved in order for the promise of this approach to be realized.

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“…From a biological standpoint, dual infection plays important roles in viral evolution, 11 , 12 the development of drug resistance, 13 , 14 host CD8 + T-cell immune responses, 15 , 16 and neutralizing antibody responses. 17 – 20 However, the impact of dual infection on HIV disease progression remains controversial.…”

Section: Introductionmentioning

confidence: 99%

Dual Infection Contributes to Rapid Disease Progression in Men Who Have Sex With Men in China

Luan

Han

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Association between Cellular Immune Activation, Target Cell Frequency, and Risk of Human Immunodeficiency Virus Type 1 Superinfection

Cited by 4 publications

References 45 publications

Breakthrough of SIV strain smE660 challenge in SIV strain mac239-vaccinated rhesus macaques despite potent autologous neutralizing antibody responses

Breakthrough of SIV strain smE660 challenge in SIV strain mac239-vaccinated rhesus macaques despite potent autologous neutralizing antibody responses

Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies

Dual Infection Contributes to Rapid Disease Progression in Men Who Have Sex With Men in China

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