Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection

French, Martyn A.; Abudulai, Laila N.; Fernández, Sonia

doi:10.3390/vaccines1030328

Cited by 24 publications

(28 citation statements)

References 96 publications

(123 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous studies have demonstrated that higher serum/plasma levels or avidity of IgG antibodies against HIV-1 Gag proteins are associated with slower progression of HIV disease (reviewed in (11)). However, to our knowledge, this is the first study to show an association between the functional activity of an IgG antibody response against HIV Gag proteins and natural control of HIV infection.…”

Section: Discussionmentioning

confidence: 99%

“…Studies in simian-human immunodeficiency virus (SHIV)-infected macaques have shown that human monoclonal antibodies against HIV-1 Env antigens suppress replication of SHIV and are capable of inducing long-term suppression of SHIV infection in a subset of animals (9, 10). Numerous studies have also demonstrated that IgG antibodies against HIV-1 Gag proteins are associated with slower progression of HIV disease (reviewed in (11)) but it is unclear what role, if any, these antibodies play in controlling HIV-1 replication.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Viremic HIV Controllers Exhibit High Plasmacytoid Dendritic Cell–Reactive Opsonophagocytic IgG Antibody Responses against HIV-1 p24 Associated with Greater Antibody Isotype Diversification

Tjiam

Taylor

Morshidi

et al. 2015

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Identifying the mechanisms of natural control of HIV-1 infection could lead to novel approaches to prevent or cure HIV infection. Several studies have associated natural control of HIV-1 infection with IgG antibodies against HIV-1 Gag proteins (e.g. p24) and/or production of IgG2 antibodies against HIV-1 proteins. These antibodies likely exert their effect by activating anti-viral effector cell responses rather than virus neutralization. We hypothesized that an opsonophagocytic IgG antibody response against HIV-1 p24 that activates plasmacytoid dendritic cells (pDCs) through FcγRIIa would be associated with control of HIV and that this would be enhanced by antibody isotype diversification. Using the Gen2.2 pDC cell line, we demonstrated that pDC-reactive opsonophagocytic IgG antibody responses against HIV-1 p24 were higher in HIV controllers (HIV RNA <2000 copies/mL) than non-controllers (HIV RNA >10,000 copies/mL) particularly in controllers with low but detectable viremia (HIV RNA 75–2000 copies/mL). Opsonophagocytic antibody responses correlated with plasma levels of IgG1 and IgG2 anti-HIV-1 p24 and notably, correlated inversely with plasma HIV RNA levels in viremic HIV patients. Phagocytosis of these antibodies was mediated via FcγRIIa. Isotype diversification (towards IgG2) was greatest in HIV controllers and depletion of IgG2 from immunoglobulin preparations indicated that IgG2 antibodies to HIV-1 p24 do not enhance phagocytosis, suggesting that they enhance other aspects of antibody function, such as antigen opsonization. Our findings emulate those for pDC-reactive opsonophagocytic antibody responses against coxsackie, picorna and influenza viruses and demonstrate a previously undefined immune correlate of HIV-1 control that may be relevant to HIV vaccine development.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Viremic HIV Controllers Exhibit High Plasmacytoid Dendritic Cell–Reactive Opsonophagocytic IgG Antibody Responses against HIV-1 p24 Associated with Greater Antibody Isotype Diversification

Tjiam

Taylor

Morshidi

et al. 2015

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Numerous studies have associated slower disease progression with higher serum levels of HIV-1 Gag-specific IgG antibodies [reviewed in (24)]. We next, hypothesized that Tfh1 responses impact SPVL by driving the production of HIV-specific IgG antibodies.…”

Section: Resultsmentioning

confidence: 98%

Frequencies of circulating Th1-biased T follicular helper cells in acute HIV-1 infection correlate with the development of HIV-specific antibody responses and lower set point viral load

Baiyegunhi¹,

Ndlovu²,

Ogunshola

et al. 2018

Preprint

View full text Add to dashboard Cite

Word count:243) 24Despite decades of focused research, the field has yet to develop a prophylactic vaccine. In the 25 RV144 vaccine trial, non-neutralizing antibody responses were identified as a correlate for 26 prevention of HIV acquisition. However, factors that predict the development of such antibodies 27 are not fully elucidated. We sought to define the contribution of circulating T follicular helper 28 (cTfh) cell subsets to the development of non-neutralizing antibodies in HIV-1 clade C infection. 29Study participants were recruited from an acute HIV-1 clade C infection cohort. Plasma anti-30 gp41, -gp120, -p24 and -p17 antibodies were screened using a customized multivariate Luminex 31 assay. Phenotypic and functional characterization of cTfh were performed using HLA class II 32 tetramers and intracellular cytokine staining. In this study, we found that acute HIV-1 clade C 33 infection skewed differentiation of functional cTfh subsets towards increased Tfh1 (p=0.02) and 34Tfh2 (p<0.0001) subsets, with a concomitant decrease in overall Tfh1-17 (that shares both Tfh1 35 and Tfh17 properties) (p=0.01) and Tfh17 subsets (p<0.0001) compared to HIV negative 36 subjects. Interestingly, the frequencies of Tfh1 during acute infection (5.0-8.0 weeks post-37 infection) correlated negatively with set point viral load (p=0.03, r=-60) and were predictive of 38 p24-specific plasma IgG titers at one year of infection (p=0.003, r=0.85). Taken together, our 39 results suggest that circulating the Tfh1 subset plays an important role in the development of 40 anti-HIV antibody responses and contributes to HIV suppression during acute HIV-1 infection. 41 These results have implications for vaccine studies aimed at inducing long lasting anti-HIV 42 antibody responses. 43 44 45 3

show abstract

“…This increase may be due to class switching which induces IgG subclasses. Several cytokines have been reported to specifically induce each IgG subclass . For example, IgG3 is induced by interferon (IFN)‐γ .…”

Section: Discussionmentioning

confidence: 99%

Allergy inhibitory receptor‐1 inhibits autoantibody production via upregulation of apoptotic debris clearance by macrophages

et al. 2018

View full text Add to dashboard Cite

Aim: Allergy inhibitory receptor-1 (Allergin-1) is a newly identified immune regulatory molecule thought to influence autoantibody production. Autoantibody production, like that observed in Allergin-1-deficient mice, is crucial in the pathogenesis of several autoimmune diseases such as systemic lupus erythematosus. The purpose of this study is to clarify the regulatory role of Allergin-1-mediated autoantibody production using a murine model of thymocytic anaphylaxis.Methods: C57BL/6 (WT) and Allergin-1-deficient mice were treated with apoptotic cells from naive thymocytes stimulated by dexamethasone. Antibody titers of total or immunoglobulin G (IgG) subclass of anti-double-stranded DNA (anti-dsDNA) and anti-histone antibody from serum were measured using an enzyme-linked immunosorbent assay. Macrophages from wild-type (WT) or Allergin-1-deficient mice were co-cultured with fluorescence-labeled apoptotic thymocytes or fluorogenic reagent and resultant phagocytic activity was quantified by with flow cytometry. Results:After apoptotic cells injection, antibody titers of total and IgG3 anti-dsDNA and total anti-histone from serum were significantly increased in Allergin-1-deficient versus WT mice. Phagocytic activity was significantly lower in macrophages from Allergin-1-deficient mice versus WT mice.Conclusion: Allergin-1 might play an inhibitory role in autoantibody production via upregulation of macrophage phagocytosis.

show abstract

Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection

Cited by 24 publications

References 96 publications

Viremic HIV Controllers Exhibit High Plasmacytoid Dendritic Cell–Reactive Opsonophagocytic IgG Antibody Responses against HIV-1 p24 Associated with Greater Antibody Isotype Diversification

Viremic HIV Controllers Exhibit High Plasmacytoid Dendritic Cell–Reactive Opsonophagocytic IgG Antibody Responses against HIV-1 p24 Associated with Greater Antibody Isotype Diversification

Frequencies of circulating Th1-biased T follicular helper cells in acute HIV-1 infection correlate with the development of HIV-specific antibody responses and lower set point viral load

Allergy inhibitory receptor‐1 inhibits autoantibody production via upregulation of apoptotic debris clearance by macrophages

Contact Info

Product

Resources

About