Mining HIV controllers for broad and functional antibodies to recognize and eliminate HIV-infected cells

Rossignol, Evan; Dugast, Anne‐Sophie; Compere, Hacheming; Cottrell, Christopher A.; Copps, Jeffrey; Lin, Shu; Cizmeci, Deniz; Seaman, Michael S.; Ackerman, Margaret E.; Ward, Andrew B.; Alter, Galit; Jülg, Boris

doi:10.1016/j.celrep.2021.109167

Cited by 12 publications

(7 citation statements)

References 97 publications

(120 reference statements)

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“…Fewer, or deletion of, PNGS in V1V2 suggested that the V3 loop may be selectively exposed and accessible on the cell surface. The slight fluctuation of genetic distance in the V3 region in our experiment confirmed that the conformational change of Env during virus assembly was inherently complex, as well as dynamic, on the cell surface ( Rossignol et al., 2021 ). The tetrapeptide of the V3 region is the binding site for the host to induce neutralizing antibodies and CTL reaction known to affect viral fusion and entry and determine the usage of co-receptors ( Bowder et al., 2018 ; Behrens et al., 2021 ).…”

Section: Discussionsupporting

confidence: 73%

Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time

Wang

Liang

Huang

et al. 2022

Front. Cell. Infect. Microbiol.

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The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. Fifty-nine full-length Env gene fragments were derived from four plasma samples sequentially harvested from the patient between 2016 and 2020. Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. Further, 24 functional Env-pseudotyped viruses were generated based on Env gene sequences. While all 24 Env-pseudotyped viruses remained sensitive to concurrent and subsequent autologous plasma, as well as bNAbs, including 10E8, VRC01, and 12A21, Env-pseudotyped viruses corresponding to later sampling time were increasingly more resistant to autologous plasma and bNAbs. All 24 Env-pseudotyped viruses were resistant to bNAbs 2G12, PGT121, and PGT135. The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. Immune escape mutants resulted in increased resistance to bNAb targeting of different epitopes. Our study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs.

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Section: Discussionsupporting

confidence: 73%

Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time

Wang

Liang

Huang

et al. 2022

Front. Cell. Infect. Microbiol.

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“…HIV is characterized by rapid evolution within and among infected individuals ( 26 ); which increases during chronic infection ( 27 – 29 ). This diversity presents a challenge for passive immunization strategies, as bNAbs targeting common Env epitopes would need to neutralize the transmitted/founder (TF) viruses for prophylaxis ( 5 , 30 ), as well as the variants that emerge in the face of immune pressure and antiretroviral therapy (ART) for therapeutic or cure applications ( 31 , 32 ). Considering the diverse bNAb biophysical properties and virus diversity, identification and characterization of the most suitable bNAbs for potential clinical use is a critical scientific goal.…”

Section: Introductionmentioning

confidence: 99%

Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection

Mandizvo

Gumede

Ndlovu

et al. 2022

J Virol

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“…It has been proposed that several Fc-mediated mechanisms, including ADCC, antibody-dependent cellular phagocytosis (ADCP), antibody-dependent complement deposition (ADCD), aggregation and immune activation, participate in HIV inhibition (Figs. 1B, 2) [14,[33][34][35][36][37]. In addition, viruses can be directly opsonized by phagocytosis via Ab and FcR binding.…”

Section: Antibodies and The Pleiotropic Function Of The Humoral Respo...mentioning

confidence: 99%

Fc receptors and the diversity of antibody responses to HIV infection and vaccination

Lin

Carapito

et al. 2022

Genes Immun

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The development of an effective vaccine against HIV is desperately needed. The successive failures of HIV vaccine efficacy trials in recent decades have shown the difficulty of inducing an appropriate protective immune response to fight HIV. Different correlates of antibody parameters associated with a decreased risk of HIV-1 acquisition have been identified. However, these parameters are difficult to reproduce and improve, possibly because they have an intricate and combined action. Here, we describe the numerous antibody (Ab) functions associated with HIV-1 protection and report the interrelated parameters regulating their complex functions. Indeed, besides neutralizing and Fc-mediated activity, additional factors such as Ab type, concentration and kinetics of induction, and Fc-receptor expression and binding capacity also influence the protective effect conferred by Abs. As these parameters were described to be associated with ethnicity, age and sex, these additional factors must be considered for the development of an effective immune response. Therefore, future vaccine designs need to consider these multifaceted Ab functions together with the demographic attributes of the patient populations.

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Mining HIV controllers for broad and functional antibodies to recognize and eliminate HIV-infected cells

Cited by 12 publications

References 97 publications

Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time

Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time

Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection

Fc receptors and the diversity of antibody responses to HIV infection and vaccination

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