HIV Vaccine efficacy trial: Glimmers of hope and the potential role of antibody-dependent cellular cytotoxicity

Wren, Leia; Kent, Stephen J.

doi:10.4161/hv.7.4.14123

Cited by 22 publications

(16 citation statements)

References 94 publications

(130 reference statements)

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“…50 This led some investigators to suggest that ADCC was the mechanism of protection, and that ADCC-competent anti-viral Abs may be sufficient for protection. 51 These hypotheses are supported by the observation that the protective capacity of BnAb b12 is diminished when a version of the Ab that mediates no ADCC is passively transferred to rhesus macaques prior to exposure to SHIV. 52 Additional support for this possibility comes from a recent study in the rhesus macaque SHIV model of HIV-infection.…”

Section: Repertoire Freeze and Selection Of Bnabs And Other Protectivsupporting

confidence: 61%

On the benefits of sin

Parsons

Müller²,

Köhler

et al. 2013

Human Vaccines & Immunotherapeutics

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Section: Repertoire Freeze and Selection Of Bnabs And Other Protectivsupporting

confidence: 61%

On the benefits of sin

Parsons

Müller²,

Köhler

et al. 2013

Human Vaccines & Immunotherapeutics

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“…It is conceivable that the NAb titers seen in HIV-2 infection prevent further superinfection with other HIV-2 strains; this is not an uncommon occurrence in HIV-1 (reviewed in references 16 and 75) but has not been extensively described or investigated in HIV-2. The role of other antibody-dependent effector functions, such as complement-mediated lysis (3) or antibody-dependent cellular toxicity (79), is unknown in HIV-2 infection and warrants investigation within this model. Our findings also add to mounting evidence that the potential for adaptive selection and escape from host immunity may be limited in HIV-2 infection, which may underlie the lower VLs and slower disease progression observed in HIV-2-infected individuals.…”

Section: Discussionmentioning

confidence: 99%

Potent Autologous and Heterologous Neutralizing Antibody Responses Occur in HIV-2 Infection across a Broad Range of Infection Outcomes

Silva

Aasa-Chapman

Cotten

et al. 2012

J Virol

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Few studies have explored the role of neutralizing antibody (NAb) responses in controlling HIV-2 viremia and disease progression. Using a TZM-bl neutralization assay, we assessed heterologous and autologous NAb responses from a community cohort of HIV-2-infected individuals with a broad range of disease outcomes in rural Guinea-Bissau. All subjects (n = 40) displayed exceptionally high heterologous NAb titers (50% inhibitory plasma dilution or 50% inhibitory concentration [IC(50)], 1:7,000 to 1:1,000,000) against 5 novel primary HIV-2 envelopes and HIV-2 7312A, whereas ROD A and 3 primary envelopes were relatively resistant to neutralization. Most individuals also showed high autologous NAb against contemporaneous envelopes (78% of plasma-envelope combinations in 69 envelopes from 21 subjects), with IC(50)s above 1:10,000. No association between heterologous or autologous NAb titer and greater control of HIV-2 was found. A subset of envelopes was found to be more resistant to neutralization (by plasma and HIV-2 monoclonal antibodies). These envelopes were isolated from individuals with greater intrapatient sequence diversity and were associated with changes in potential N-linked glycosylation sites but not CD4 independence or CXCR4 use. Plasma collected from up to 15 years previously was able to potently neutralize recent autologous envelopes, suggesting a lack of escape from NAb and the persistence of neutralization-sensitive variants over time, despite significant NAb pressure. We conclude that despite the presence of broad and potent NAb responses in HIV-2-infected individuals, these are not the primary forces behind the dichotomous outcomes observed but reveal a limited capacity for adaptive selection and escape from host immunity in HIV-2 infection.

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“…Several other investigations support a role for ADCC in protection from HIV infection and disease progression, demonstrating the activity at higher levels in HIV-exposed seronegative individuals, elite controllers, and rhesus macaques protected through vaccination (9,19,29). Moreover, the recent RV144 Thai vaccine trial, which provided partial protection from HIV infection, induced anti-HIV ADCC-competent Abs (35). Coinciding with the increasing evidence for ADCC as a protective anti-HIV immune response, it is also well established that NK cell responsiveness decreases with progressive HIV infection (13,27), ultimately decreasing the ability of NK cells to mediate ADCC.…”

mentioning

confidence: 99%