Antibody-dependent cellular cytotoxicity in HIV infection

Forthal, Donald N.; Finzi, Andrés

doi:10.1097/qad.0000000000002011

Cited by 82 publications

(82 citation statements)

References 164 publications

(175 reference statements)

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“…Notably, peptide S1-57 competed the neutralizing activity of two sera out of four sera tested ( Figure 5) (Table 1), suggesting the antibodies against this peptide play an import role in neutralizing activity. In contrast, peptide S2-13 didn't compete the neutralizing activity of the sera tested, which is inconsistent to the previous study [18]. The discrepancy might be due to the variation of the sera used.…”

Section: Discussioncontrasting

confidence: 96%

Functional mapping of B-cell linear epitopes of SARS-CoV-2 in COVID-19 convalescent population

Ling

Zhang

et al. 2020

Emerging Microbes & Infections

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Pandemic SARS-CoV-2 has caused unprecedented mortalities. Vaccine is in urgent need to stop the pandemic. Despite great progresses on SARS-CoV-2 vaccine development, the efficacy of the vaccines remains to be determined. Deciphering the interactions of the viral epitopes with the elicited neutralizing antibodies in convalescent population inspires the vaccine development. In this study, we devised a peptide array composed of 20-mer overlapped peptides of spike (S), membrane (M) and envelope (E) proteins, and performed a screening with 120 COVID-19 convalescent sera and 24 non-COVID-19 sera. We identified five SARS-CoV-2-specific dominant epitopes that reacted with above 40% COVID-19 convalescent sera. Of note, two peptides non-specifically interacted with most of the non-COVID-19 sera. Neutralization assay indicated that only five sera completely blocked viral infection at the dilution of 1:200. By using a peptide-compete neutralizing assay, we found that three dominant epitopes partially competed the neutralization activity of several convalescent sera, suggesting antibodies elicited by these epitopes played an important role in neutralizing viral infection. The epitopes we identified in this study may serve as vaccine candidates to elicit neutralizing antibodies in most vaccinated people or specific antigens for SARS-CoV-2 diagnosis.

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Section: Discussioncontrasting

confidence: 96%

Functional mapping of B-cell linear epitopes of SARS-CoV-2 in COVID-19 convalescent population

Ling

Zhang

et al. 2020

Emerging Microbes & Infections

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“…It is now well established that the conformation of Env at the cell surface influences antibody binding and ADCC responses (38)(39)(40). Nonneutralizing antibodies and bNAbs target different Env conformations, with most bNAbs preferentially recognizing Env in its "closed" conformation (state 1) (36), whereas the nNAbs used here target epitopes that are only exposed upon Env interaction with CD4 (9,33,37,42).…”

Section: Resultsmentioning

confidence: 99%

Antibody-Induced Internalization of HIV-1 Env Proteins Limits Surface Expression of the Closed Conformation of Env

Anand

Grover

Tolbert

et al. 2019

J Virol

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To minimize immune responses against infected cells, HIV-1 limits the surface expression of its envelope glycoprotein (Env). Here, we demonstrate that this mechanism is specific for the Env conformation and affects the efficiency of antibody-dependent cellular cytotoxicity (ADCC). Using flow cytometry and confocal microscopy, we show that broadly neutralizing antibodies (bNAbs) targeting the "closed" conformation of Env induce its internalization from the surface. In contrast, non-neutralizing antibodies (nNAbs) are displayed on the cell surface for prolonged period of times. The bNAb-induced Env internalization can be decreased by blocking dynamin function, which translates into higher susceptibilities of infected cells to ADCC. Our results suggest that antibody-mediated Env internalization is a mechanism used by HIV-1 to evade immune responses against the "closed" conformation of Env expressed on HIV-1-infected cells.IMPORTANCE HIV-1 has evolved to acquire several strategies to limit the exposure of its envelope glycoproteins (Env) on the surface of infected cells. In this study, we show that antibody-induced Env internalization is conformation specific and reduces the susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). Thus, a better understanding of this mechanism might help develop antibodies with improved capacities to mediate ADCC.

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“…As a consequence, different Env conformations can be involved according to the infection stage, and therefore the recognition of different specific epitopes by Abs may impact the ADCC results (137). Moreover, caution needs to be taken to ensure that the identified Abs effectively target infected cells and not uninfected cells that have captured HIV Env via their CD4 receptor (138)(139)(140). Therefore, identifying the viral epitopes on infected cells involved in ADCC is critical.…”

Section: Antibody-dependent Cellular Cytotoxicitymentioning

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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Antibody-dependent cellular cytotoxicity in HIV infection

Cited by 82 publications

References 164 publications

Functional mapping of B-cell linear epitopes of SARS-CoV-2 in COVID-19 convalescent population

Functional mapping of B-cell linear epitopes of SARS-CoV-2 in COVID-19 convalescent population

Antibody-Induced Internalization of HIV-1 Env Proteins Limits Surface Expression of the Closed Conformation of Env

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

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