Temporal variation in HIV-specific IgG subclass antibodies during acute infection differentiates spontaneous controllers from chronic progressors

Sadanand, Saheli; Das, Jishnu; Chung, Amy W.; Schoen, Matthew K.; Lane, Sophie; Suscovich, Todd J.; Streeck, Hendrik; Smith, Davey M.; Little, Susan J.; Lauffenburger, Douglas A.; Richman, Douglas D.; Alter, Galit

doi:10.1097/qad.0000000000001716

Cited by 40 publications

(44 citation statements)

References 41 publications

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“…Antibody responses in the first months of HIV-1 infection are governed by non-neutralizing antibodies directed against Env (175). While initially thought to be ineffective, these early antibodies display some viral inhibition, while higher ADCC activity of vaccine-induced IgG has been associated with reduced peak viral load in macaque SHIV trials (176)(177)(178). The isotypes that predominate during this time are IgM followed by classswitching to IgG and IgA (179,180).…”

Section: Antibody Isotypes and Subclasses In Hiv-1mentioning

confidence: 99%

“…During acute infection, IgG3 is elicited first in the IgG subclass response but eventually is surpassed by higher IgG1 titers against Env (187). Multiple studies have associated HIV-specific IgG3 with viral control and enhanced Fc-functions (172,178,188,189). IgG1 and IgG2 against internal HIV-1 p24 protein have also associated with viral control though the mechanisms are still not understood (190,191).…”

Section: Antibody Isotypes and Subclasses In Hiv-1mentioning

confidence: 99%

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An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

McLean

Kent

et al. 2019

Front. Immunol.

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Mycobacterium tuberculosis (Mtb) resides in a quarter of the world's population and is the causative agent for tuberculosis (TB), the most common infectious reason of death in humans today. Although cellular immunity has been firmly established in the control of Mtb, there is growing evidence that antibodies may also modulate the infection. More specifically, certain antibody features are associated with inflammation and are divergent in different states of human infection and disease. Importantly, TB impacts not just the healthy but also those with chronic conditions. While HIV represents the quintessential comorbid condition for TB, recent epidemiological evidence shows that additional chronic conditions such as diabetes and kidney disease are rising. In fact, the prevalence of diabetes as a comorbid TB condition is now higher than that of HIV. These chronic diseases are themselves independently associated with proinflammatory immune states that encompass antibody profiles. This review discusses isotypes, subclasses, post-translational modifications and Fc-mediated functions of antibodies in TB infection and in the comorbid chronic conditions of HIV, diabetes, and kidney diseases. We propose that inflammatory antibody profiles, which are a marker of active TB, may be an important biomarker for detection of TB disease progression within comorbid individuals. We highlight the need for future studies to determine which inflammatory antibody profiles are the consequences of comorbidities and which may potentially contribute to TB reactivation.

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Section: Antibody Isotypes and Subclasses In Hiv-1mentioning

confidence: 99%

Section: Antibody Isotypes and Subclasses In Hiv-1mentioning

confidence: 99%

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

McLean

Kent

et al. 2019

Front. Immunol.

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“…Considerable evidence suggests that steering immune responses towards certain Ig subclasses and/or Fc modifications needs to be evaluated. HIV-1 controllers display antibody subclass profiles that are skewed towards IgG1 or IgG3 responses with the ability to coordinate several effector functions including ADCC and ADCP that suppress viral replication [ 98 – 100 ]. Similarly, immune correlates of protection in the RV144 trial have been linked to antibody effector functions [ 101 , 102 ].…”

Section: Specific Antibody Signatures Are Linked With Neutralization mentioning

confidence: 99%

Broadly neutralizing antibodies: What is needed to move from a rare event in HIV-1 infection to vaccine efficacy?

2018

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The elicitation of broadly neutralizing antibodies (bnAbs) is considered crucial for an effective, preventive HIV-1 vaccine. Led by the discovery of a new generation of potent bnAbs, the field has significantly advanced over the past decade. There is a wealth of knowledge about the development of bnAbs in natural infection, their specificity, potency, breadth and function. Yet, devising immunogens and vaccination regimens that evoke bnAb responses has not been successful. Where are the roadblocks in their development? What can we learn from natural infection, where bnAb induction is possible but rare? Herein, we will reflect on key discoveries and discuss open questions that may bear crucial insights needed to move towards creating effective bnAb vaccines.

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“…Early primary immune responses to infections are dominated by IgM while IgG emerges later and in secondary responses upon re-infection. The IgG response is initiated by IgG3 followed by IgG1, both of which are considered anti-viral subclasses (118)(119)(120)(121). However, how each of the four human IgG subclasses activate TRIM21 in the cytosol when bound to viruses has yet to be addressed in detail.…”

Section: Discussionmentioning

confidence: 99%

TRIM21—From Intracellular Immunity to Therapy

et al. 2019

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Tripartite motif containing-21 (TRIM21) is a cytosolic ubiquitin ligase and antibody receptor that provides a last line of defense against invading viruses. It does so by acting as a sensor that intercepts antibody-coated viruses that have evaded extracellular neutralization and breached the cell membrane. Upon engagement of the Fc of antibodies bound to viruses, TRIM21 triggers a coordinated effector and signaling response that prevents viral replication while at the same time inducing an anti-viral cellular state. This dual effector function is tightly regulated by auto-ubiquitination and phosphorylation. Therapeutically, TRIM21 has been shown to be detrimental in adenovirus based gene therapy, while it may be favorably utilized to prevent tau aggregation in neurodegenerative disorders. In addition, TRIM21 may synergize with the complement system to block viral replication as well as transgene expression. TRIM21 can also be utilized as a research tool to deplete specific proteins in cells and zebrafish embryos. Here, we review our current biological understanding of TRIM21 in light of its versatile functions.

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Temporal variation in HIV-specific IgG subclass antibodies during acute infection differentiates spontaneous controllers from chronic progressors

Cited by 40 publications

References 41 publications

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

Broadly neutralizing antibodies: What is needed to move from a rare event in HIV-1 infection to vaccine efficacy?

TRIM21—From Intracellular Immunity to Therapy

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