Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells
HIV-1-infected individuals raise a polyclonal antibody response targeting multiple envelope glycoprotein (Env) epitopes. Interestingly, two classes of non-neutralizing CD4-induced (CD4i) antibodies, present in the majority of HIV-1-infected individuals have been described to mediate antibody-depende...
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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/8/5/710 |
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| author | Guillaume Beaudoin-Bussières Jérémie Prévost Gabrielle Gendron-Lepage Bruno Melillo Junhua Chen Amos B. Smith III Marzena Pazgier Andrés Finzi |
| author_facet | Guillaume Beaudoin-Bussières Jérémie Prévost Gabrielle Gendron-Lepage Bruno Melillo Junhua Chen Amos B. Smith III Marzena Pazgier Andrés Finzi |
| author_sort | Guillaume Beaudoin-Bussières |
| collection | DOAJ |
| description | HIV-1-infected individuals raise a polyclonal antibody response targeting multiple envelope glycoprotein (Env) epitopes. Interestingly, two classes of non-neutralizing CD4-induced (CD4i) antibodies, present in the majority of HIV-1-infected individuals have been described to mediate antibody-dependent cellular cytotoxicity (ADCC) in the presence of small CD4 mimetic compounds (CD4mc). These antibodies recognize the coreceptor binding site (CoRBS) and the constant region one and two (C1C2 or inner domain cluster A) of the gp120. In combination with CD4mc they have been shown to stabilize an antibody-vulnerable Env conformation, known as State 2A. Here we evaluated the importance of these two families of Abs in ADCC responses by immunizing guinea pigs with gp120 immunogens that have been modified to elicit or not these types of antibodies. Underlying the importance of anti-CoRBS and anti-cluster A Abs in stabilizing State 2A, ADCC responses were only observed in the presence of these two types of CD4i antibodies. Altogether, our results suggest that these two families of CD4i antibodies must be taken into account when considering future strategies relying on the use of CD4mc to eliminate HIV-1-infected cells in vivo. |
| first_indexed | 2024-03-10T19:54:09Z |
| format | Article |
| id | doaj.art-0c75b452eb3e4759b4ce066bfa207b29 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T19:54:09Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-0c75b452eb3e4759b4ce066bfa207b292023-11-20T00:03:07ZengMDPI AGMicroorganisms2076-26072020-05-018571010.3390/microorganisms8050710Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected CellsGuillaume Beaudoin-Bussières0Jérémie Prévost1Gabrielle Gendron-Lepage2Bruno Melillo3Junhua Chen4Amos B. Smith III5Marzena Pazgier6Andrés Finzi7Centre de Recherche du CHUM, Montreal, QC H2X 0A9, CanadaCentre de Recherche du CHUM, Montreal, QC H2X 0A9, CanadaCentre de Recherche du CHUM, Montreal, QC H2X 0A9, CanadaDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104-6323, USADepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104-6323, USADepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104-6323, USAInfectious Diseases Division, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USACentre de Recherche du CHUM, Montreal, QC H2X 0A9, CanadaHIV-1-infected individuals raise a polyclonal antibody response targeting multiple envelope glycoprotein (Env) epitopes. Interestingly, two classes of non-neutralizing CD4-induced (CD4i) antibodies, present in the majority of HIV-1-infected individuals have been described to mediate antibody-dependent cellular cytotoxicity (ADCC) in the presence of small CD4 mimetic compounds (CD4mc). These antibodies recognize the coreceptor binding site (CoRBS) and the constant region one and two (C1C2 or inner domain cluster A) of the gp120. In combination with CD4mc they have been shown to stabilize an antibody-vulnerable Env conformation, known as State 2A. Here we evaluated the importance of these two families of Abs in ADCC responses by immunizing guinea pigs with gp120 immunogens that have been modified to elicit or not these types of antibodies. Underlying the importance of anti-CoRBS and anti-cluster A Abs in stabilizing State 2A, ADCC responses were only observed in the presence of these two types of CD4i antibodies. Altogether, our results suggest that these two families of CD4i antibodies must be taken into account when considering future strategies relying on the use of CD4mc to eliminate HIV-1-infected cells in vivo.https://www.mdpi.com/2076-2607/8/5/710HIV-1ADCCcluster Acoreceptor binding siteguinea pigssmall CD4 mimetics |
| spellingShingle | Guillaume Beaudoin-Bussières Jérémie Prévost Gabrielle Gendron-Lepage Bruno Melillo Junhua Chen Amos B. Smith III Marzena Pazgier Andrés Finzi Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells Microorganisms HIV-1 ADCC cluster A coreceptor binding site guinea pigs small CD4 mimetics |
| title | Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells |
| title_full | Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells |
| title_fullStr | Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells |
| title_full_unstemmed | Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells |
| title_short | Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells |
| title_sort | elicitation of cluster a and co receptor binding site antibodies are required to eliminate hiv 1 infected cells |
| topic | HIV-1 ADCC cluster A coreceptor binding site guinea pigs small CD4 mimetics |
| url | https://www.mdpi.com/2076-2607/8/5/710 |
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