Antiviral Antibodies Are Necessary for Control of Simian Immunodeficiency Virus Replication

Miller, Christopher J.; Genescà, Meritxell; Abel, Kristina; Montefiori, David C.; Forthal, Donald N.; Bost, Kristen; Li, Jun; Favre, David; McCune, Joseph M.

doi:10.1128/jvi.02444-06

Cited by 71 publications

(78 citation statements)

References 46 publications

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“…50 Nevertheless, CD20 B-cell depletion studies in SIV-infected RMs have reported a possible role for antibodies in controlling SIVmac251 replication and disease progression during SIVmac239 infection. 26,27 However, these studies both had the caveat that they used highly pathogenic SIV strains that are characterized by rapid progression to simian AIDS. Moreover, SIVmac strains (SIVmac251 and SIVmac239) are very difficult to neutralize, 51,52 so humoral immune responses may be expected to have only a limited impact on the outcome of infection.…”

Section: Discussionmentioning

confidence: 99%

“…This follow-up is significantly longer than any survival reported thus far for CD20-depletion studies. 26,27 As most of the studies were carried out with highly pathogenic SIVmac strains, the shorter duration of disease progression during such highly pathogenic infections did not allow a long-term assessment of the impact of CD20 B-cell depletion on survival.…”

Section: Discussionmentioning

confidence: 99%

“…A second study, in which rituximab was administered continuously at a higher dosage until AIDS developed, reported a significantly higher rate of disease progression in animals exhibiting complete B-cell depletion compared with those that exhibited incomplete depletion. 26 However, as the animals were infected with SIVmac239, a virus that is very difficult to neutralize, the role of neutralizing antibodies in this case remains unclear. 26 Here we reassessed the role of humoral responses in SIV infection by pretreating RMs with an anti-CD20 monoclonal antibody (Rituxan, rituximab; gift from Genentech) and inoculating with the strain SIVsmmD215 directly derived from a naturally infected sooty mangabey (SM) and that is highly susceptible to neutralization.…”

Section: Introductionmentioning

confidence: 99%

“…26 However, as the animals were infected with SIVmac239, a virus that is very difficult to neutralize, the role of neutralizing antibodies in this case remains unclear. 26 Here we reassessed the role of humoral responses in SIV infection by pretreating RMs with an anti-CD20 monoclonal antibody (Rituxan, rituximab; gift from Genentech) and inoculating with the strain SIVsmmD215 directly derived from a naturally infected sooty mangabey (SM) and that is highly susceptible to neutralization. We report that humoral immune responses have a limited ability to control SIV replication.…”

Section: Introductionmentioning

confidence: 99%

“…Only 2 such experiments have been reported thus far and their results did not permit a clear conclusion on whether antibodies play an essential role in the control of post-acute and chronic viral replication. 26,27 In the first study, a short-term depletion of CD20 cells by infusion of an anti-CD20 commercial monoclonal antibody (rituximab; Genentech, San Francisco, CA) had no significant impact on the resolution of peak viremia in SIVmac251-infected RMs. 27 However, the authors reported a temporal inverse correlation between the emergence of anti-SIVneutralizing antibodies and the control of viral replication during the post-acute phase of infection, suggesting that humoral immune responses may contribute to the control of chronic SIV replication.…”

Section: Introductionmentioning

confidence: 99%

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Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain

Gaufin

Gautam

Kasheta³

et al. 2009

Blood

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We investigated the impact of rhesus macaque (RM) B-cell depletion before inoculation with the isolate SIVsmmD215. Seven RMs were treated every 3 weeks with 50 mg/kg of an anti-CD20 antibody (rituximab) starting 7 days before inoculation for 2 (n ‫؍‬ 4) and 5 (n ‫؍‬ 3) months. Four control animals received no antibody. Three animals were completely depleted of CD20 ؉ B cells, but 4 were only partially depleted of CD20 cells in the LNs and intestine. The decrease in antibody production was consistent with the efficacy of tissue CD20 depletion. Seroconversion and neutralizing antibody production was significantly delayed in animals showing complete tissue CD20 depletion and remained at low titers in all CD20-depleted RMs. Surprisingly, there was no significant difference in acute or chronic viral loads between CD20-depleted and control animal groups. There was a tendency for lower viral set points in CD20-depleted animals. At 6 weeks after inoculation, cellular immune responses were significantly stronger in CD20-depleted animals than in controls. There was no significant difference in survival between CD20-depleted and control animals. Our data suggest that a deficiency of Ab responses did not markedly affect viral replication or disease progression and that they may be compensated by more robust cellular responses. (Blood. 2009; 113:4250-4261)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain

Gaufin

Gautam

Kasheta³

et al. 2009

Blood

Self Cite

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Innovative Approaches to Develop Prophylactic and Therapeutic Vaccines against HIV/AIDS

Cafaro

Macchia

Maggiorella

et al. 2009

Pharmaceutical Biotechnology

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The acquired immunodeficiency syndrome (AIDS) emerged in the human population in the summer of 1981. According to the latest United Nations estimates, worldwide over 33 million people are infected with human immunodeficiency virus (HIV) and the prevalence rates continue to rise globally. To control the alarming spread of HIV, an urgent need exists for developing a safe and effective vaccine that prevents individuals from becoming infected or progressing to disease. To be effective, an HIV/AIDS vaccine should induce broad and long-lasting humoral and cellular immune responses, at both mucosal and systemic level. However, the nature of protective immune responses remains largely elusive and this represents one of the major roadblocks preventing the development of an effective vaccine. Here we summarize our present understanding of the factors responsible for resistance to infection or control of progression to disease in human and monkey that may be relevant to vaccine development and briefly review recent approaches which are currently being tested in clinical trials. Finally, the rationale and the current status of novel strategies based on nonstructural HIV-1 proteins, such as Tat, Nef and Rev, used alone or in combination with modified structural HIV-1 Env proteins are discussed.

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Humanized Mouse Versus Non-human Primate Models of HIV-1 Infection

Wood

2014

Humanized Mice for HIV Research

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Antiviral Antibodies Are Necessary for Control of Simian Immunodeficiency Virus Replication

Cited by 71 publications

References 46 publications

Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain

Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain

Innovative Approaches to Develop Prophylactic and Therapeutic Vaccines against HIV/AIDS

Humanized Mouse Versus Non-human Primate Models of HIV-1 Infection

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