FCGR2A and FCGR3A Genotypes in Human Immunodeficiency Virus Mother-to-Child Transmission

Milligan, Caitlin; Richardson, Barbra A.; John‐Stewart, Grace; Nduati, Ruth; Overbaugh, Julie

doi:10.1093/ofid/ofv149

Cited by 11 publications

(19 citation statements)

References 36 publications

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“…The lack of consistent effect of different FcγR genotypes on susceptibility to HIV acquisition, viral control, or disease progression in the current study, is largely in agreement with several studies suggesting that FcγRIIA 9,11,12,15 and FcγRIIIA 10,12 do not play a significant role in these processes. Some of the results presented here indicate that maximum exposure to both homozygous high affinity FcγRIIA and FcγRIIIA genotypes could increase rate of HIV acquisition, with the caveat that those with exposure level 4 represented a very small group of individuals in both Rwanda and Zambia.…”

Section: Discussionsupporting

confidence: 92%

“…The distribution of FcγRIIA and FcγRIIIA alleles in either HIV-uninfected or infected individuals has not been previously described for Rwanda or Zambia, and are consistent with those in other countries reported in the literature 11,15,27,28 . In a Tanzanian cohort of 174 HIVuninfected and 99 HIV-infected individuals, similar FcγRIIA and FcγRIIIA genotype distributions were observed among HIV-uninfected individuals, with no difference by biological sex, FcγRIIA (p = 0.76) or FcγRIIIA (p = 0.88).…”

Section: Discussionsupporting

confidence: 90%

“…A recent study in South Africa contrasted this finding and reported that maternal genotype was important and showed that FcγRIIA RR genotype was associated with increased odds of transmission and that the FcγRIIIA V allele was associated with reduced MTCT risk 14 . In another cohort of Kenyan mother-infant pairs, infant genotype was not associated with infection or disease progression, however maternal genotype, specifically FcγRIIIA VF heterozygosity, was associated with increased risk of MTCT during the early breastfeeding period 15 . Finally, a study that included multiple modes of transmission (sexual and intravenous drug use), found an association between the high affinity FcγRIIIA VV genotype and presence of HIV infection, but the association was weakly significant and included a small study population 11 .…”

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

Fc-gamma receptor IIA and IIIA variants in two African cohorts: Lack of consistent impact on heterosexual HIV acquisition, viral control, and disease progression

et al. 2018

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Human Fc-gamma receptors (FcγRs) FcγRIIA and FcγRIIIA contain amino acid variants with both high and low affinities for IgG that modulate antibody-mediated effector functions. Recent HIV vaccine trials suggested that these FcγR variants can influence susceptibility to HIV infection, which prompted us to fully assess the role of FcγR variants on HIV acquisition, viral control, and disease progression in two longitudinal heterosexual transmission cohorts with HIV subtypes A and C as the major circulating viruses. For 836 participants, molecular genotyping resolved genetic variations encoding the FcγRIIA (131H/R) and FcγRIIIA (158V/F) single nucleotide polymorphisms. Kaplan-Meier curves, Cox proportional hazards models, and linear regression models did not reveal any clear or consistent FcγR association with time to HIV acquisition, viral load in early infection, or extent of CD4+ T-cell decline over time after infection. Overall, previous epidemiological findings on FcγR variants and vaccine efficacy are not readily applicable to heterosexual HIV transmission.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 95%

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Fc-gamma receptor IIA and IIIA variants in two African cohorts: Lack of consistent impact on heterosexual HIV acquisition, viral control, and disease progression

et al. 2018

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“…Furthermore, although it has not yet been thoroughly investigated, there is evidence that FcγR polymorphisms are associated with mother-to-child transmission of HIV. Mothers with the FcγRIIIa-158V allele have enhanced binding affinity for IgG and ADCC capacity, which reduces the susceptibility of their fetuses to HIV infection and significantly reduces the chance of mother-tochild transmission during both the intrapartum and in utero periods compared with the FcγRIIIa-158F allele (110,111).…”

Section: Fc-receptor: the Cellular Counterpart For Antibody-mediated mentioning

confidence: 99%

Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

Dispinseri

Iannone

et al. 2019

Front. Immunol.

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Antibodies (Abs) are the major component of the humoral immune response and a key player in vaccination. The precise Ab-mediated inhibitory mechanisms leading to in vivo protection against HIV have not been elucidated. In addition to the desired viral capture and neutralizing Ab functions, complex Ab-dependent mechanisms that involve engaging immune effector cells to clear infected host cells, immune complexes, and opsonized virus have been proposed as being relevant. These inhibitory mechanisms involve Fc-mediated effector functions leading to Ab-dependent cellular cytotoxicity, phagocytosis, cell-mediated virus inhibition, aggregation, and complement inhibition. Indeed, the decreased risk of infection observed in the RV144 HIV-1 vaccine trial was correlated with the production of non-neutralizing inhibitory Abs, highlighting the role of Ab inhibitory functions besides neutralization. Moreover, Ab isotypes and subclasses recognizing specific HIV envelope epitopes as well as pecular Fc-receptor polymorphisms have been associated with disease progression. These findings further support the need to define which Fc-mediated Ab inhibitory functions leading to protection are critical for HIV vaccine design. Herein, based on our previous review Su & Moog Front Immunol 2014, we update the different inhibitory properties of HIV-specific Abs that may potentially contribute to HIV protection.

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“…5 HIV breastmilk transmission has been dramatically reduced by initiating antiretroviral therapy (ART) early in pregnant women and maintaining treatment throughout lactation. 6 However, 30% of infected women do not adequately comply with ART. 7 In addition, 30%-40% of HIV-infected pregnant or breastfeeding women still do not have access to ART.…”

Section: Introductionmentioning

confidence: 99%

Oral Coadministration of an Intramuscular DNA/Modified Vaccinia Ankara Vaccine for Simian Immunodeficiency Virus Is Associated with Better Control of Infection in Orally Exposed Infant Macaques

Curtis

Walter

Nabi

et al. 2019

AIDS Research and Human Retroviruses

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The majority of human immunodeficiency virus (HIV) type 1 infections in infants are acquired orally through breastfeeding. Toward development of a pediatric HIV vaccine to prevent breastmilk transmission, we tested the efficacy of a simultaneous oral and intramuscular (IM) vaccination regimen for preventing oral simian immunodeficiency virus (SIV) transmission in infant rhesus macaques. Two groups of neonatal macaques were immunized with DNA encoding SIV virus-like particles (DNA-SIV) on weeks 0 and 3, then boosted with modified vaccinia Ankara (MVA) virus expressing SIV antigens (MVA-SIV) on weeks 6 and 9. One group was prime/boosted by the IM route only. Another group was immunized with DNA by both the IM and topical oral (O) buccal routes, and boosted with MVA-SIV by both the IM and sublingual (SL) routes. A third group of control animals received saline by O + IM routes on weeks 0 and 3, and empty MVA by SL + IM routes on weeks 6 and 9. On week 12, infants were orally challenged once weekly with SIV mac251 until infected. The vaccine regimen that included oral routes resulted in reduced peak viremia. The rate of infection acquisition in vaccinated infants was found to be associated with prechallenge intestinal immunoglobulin G (IgG) responses to SIV gp120 and V1V2. Peak viremia was inversely correlated with postinfection intestinal IgG responses to gp120, gp41, and V1V2. These results suggest that codelivery of a pediatric HIV vaccine by an oral route may be superior to IM-only regimens for generating mucosal antibodies and preventing HIV breastmilk transmission in neonates.

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FCGR2A and FCGR3A Genotypes in Human Immunodeficiency Virus Mother-to-Child Transmission

Cited by 11 publications

References 36 publications

Fc-gamma receptor IIA and IIIA variants in two African cohorts: Lack of consistent impact on heterosexual HIV acquisition, viral control, and disease progression

Fc-gamma receptor IIA and IIIA variants in two African cohorts: Lack of consistent impact on heterosexual HIV acquisition, viral control, and disease progression

Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

Oral Coadministration of an Intramuscular DNA/Modified Vaccinia Ankara Vaccine for Simian Immunodeficiency Virus Is Associated with Better Control of Infection in Orally Exposed Infant Macaques

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