394 Inclusion of cytomegalovirus viral Fc gamma receptors in a glycoprotein B protein subunit vaccine improves Fc-mediated effector responses
Objectives/Goals: We hypothesized that adding cytomegalovirus (CMV) viral Fc gamma receptors (vFcγRs) to a glycoprotein B (gB) protein subunit vaccine would improve vaccine-elicited Fc mediated effector functions such as antibody dependent cellular phagocytosis (ADCP) and cytotoxicity (ADCC), over g...
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| Format: | Article |
| Language: | English |
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Cambridge University Press
2025-04-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866124010136/type/journal_article |
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| author | Claire Otero Mackensie Gross Savannah Herbek Megan Connors Philipp Kolb Sallie Permar |
| author_facet | Claire Otero Mackensie Gross Savannah Herbek Megan Connors Philipp Kolb Sallie Permar |
| author_sort | Claire Otero |
| collection | DOAJ |
| description | Objectives/Goals: We hypothesized that adding cytomegalovirus (CMV) viral Fc gamma receptors (vFcγRs) to a glycoprotein B (gB) protein subunit vaccine would improve vaccine-elicited Fc mediated effector functions such as antibody dependent cellular phagocytosis (ADCP) and cytotoxicity (ADCC), over gB subunit alone. Methods/Study Population: We immunized rabbits (n = 4 per group) at Weeks 0, 4, and 8 with 20μg gB alone or with one vFcgR (gp34, gp68, or gp95) at 20μg or 40μg, adjuvanted with squalene emusion, Addavax. Plasma from immunized rabbits was analyzed for antigen-specific IgG binding via enzyme-linked immunosorbent assays (ELISAs). ADCP was measured by conjugating whole virions to a fluorescent marker (AF647), incubating the fluorescent virus with rabbit plasma, and measuring uptake of virus by THP-1 monocytes via flow cytometry. ADCC was measured by natural killer cell degranulation via flow cytometric detection of CD107a expression following co-incubation with CMV-infected fibroblasts and rabbit plasma. Results/Anticipated Results: Each vFcγR demonstrated immunogenicity, although average vFcγR-binding IgG titers were between 4- to 10-fold higher in animals receiving the 40μg dose of each vFcγR compared to the 20μg dose. We observed similar IgG binding responses against gB among all vaccine groups. Comparing groups at peak immunogenicity (Week 10), ADCP responses were improved over gB alone by approximately twofold in animals receiving 40ug of each vFcγR. This effect was maintained across several human CMV strains with variable vFcγR genes. ADCC responses were undetectable in all animals immunized with gB alone, yet those receiving 40μg gp34 or gp95 demonstrated detectable ADCC. Discussion/Significance of Impact: HCMV-specific ADCP and ADCC are associated with protection against vertical CMV transmission, so a vaccine including vFcγRs which can improve vaccine-elicited Fc-effector responses is promising toward reducing the immense global impact of congenital CMV and associated neurologic birth defects. |
| format | Article |
| id | doaj-art-7b7fc49ee0454eec9ab473f9deb8f37f |
| institution | DOAJ |
| issn | 2059-8661 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj-art-7b7fc49ee0454eec9ab473f9deb8f37f2025-08-20T02:40:51ZengCambridge University PressJournal of Clinical and Translational Science2059-86612025-04-01912112110.1017/cts.2024.1013394 Inclusion of cytomegalovirus viral Fc gamma receptors in a glycoprotein B protein subunit vaccine improves Fc-mediated effector responsesClaire Otero0Mackensie Gross1Savannah Herbek2Megan Connors3Philipp Kolb4Sallie Permar5Weill Cornell MedicineWeill Cornell MedicineWeill Cornell MedicineWeill Cornell MedicineUniversity of FreiburgWeill Cornell MedicineObjectives/Goals: We hypothesized that adding cytomegalovirus (CMV) viral Fc gamma receptors (vFcγRs) to a glycoprotein B (gB) protein subunit vaccine would improve vaccine-elicited Fc mediated effector functions such as antibody dependent cellular phagocytosis (ADCP) and cytotoxicity (ADCC), over gB subunit alone. Methods/Study Population: We immunized rabbits (n = 4 per group) at Weeks 0, 4, and 8 with 20μg gB alone or with one vFcgR (gp34, gp68, or gp95) at 20μg or 40μg, adjuvanted with squalene emusion, Addavax. Plasma from immunized rabbits was analyzed for antigen-specific IgG binding via enzyme-linked immunosorbent assays (ELISAs). ADCP was measured by conjugating whole virions to a fluorescent marker (AF647), incubating the fluorescent virus with rabbit plasma, and measuring uptake of virus by THP-1 monocytes via flow cytometry. ADCC was measured by natural killer cell degranulation via flow cytometric detection of CD107a expression following co-incubation with CMV-infected fibroblasts and rabbit plasma. Results/Anticipated Results: Each vFcγR demonstrated immunogenicity, although average vFcγR-binding IgG titers were between 4- to 10-fold higher in animals receiving the 40μg dose of each vFcγR compared to the 20μg dose. We observed similar IgG binding responses against gB among all vaccine groups. Comparing groups at peak immunogenicity (Week 10), ADCP responses were improved over gB alone by approximately twofold in animals receiving 40ug of each vFcγR. This effect was maintained across several human CMV strains with variable vFcγR genes. ADCC responses were undetectable in all animals immunized with gB alone, yet those receiving 40μg gp34 or gp95 demonstrated detectable ADCC. Discussion/Significance of Impact: HCMV-specific ADCP and ADCC are associated with protection against vertical CMV transmission, so a vaccine including vFcγRs which can improve vaccine-elicited Fc-effector responses is promising toward reducing the immense global impact of congenital CMV and associated neurologic birth defects.https://www.cambridge.org/core/product/identifier/S2059866124010136/type/journal_article |
| spellingShingle | Claire Otero Mackensie Gross Savannah Herbek Megan Connors Philipp Kolb Sallie Permar 394 Inclusion of cytomegalovirus viral Fc gamma receptors in a glycoprotein B protein subunit vaccine improves Fc-mediated effector responses Journal of Clinical and Translational Science |
| title | 394 Inclusion of cytomegalovirus viral Fc gamma receptors in a glycoprotein B protein subunit vaccine improves Fc-mediated effector responses |
| title_full | 394 Inclusion of cytomegalovirus viral Fc gamma receptors in a glycoprotein B protein subunit vaccine improves Fc-mediated effector responses |
| title_fullStr | 394 Inclusion of cytomegalovirus viral Fc gamma receptors in a glycoprotein B protein subunit vaccine improves Fc-mediated effector responses |
| title_full_unstemmed | 394 Inclusion of cytomegalovirus viral Fc gamma receptors in a glycoprotein B protein subunit vaccine improves Fc-mediated effector responses |
| title_short | 394 Inclusion of cytomegalovirus viral Fc gamma receptors in a glycoprotein B protein subunit vaccine improves Fc-mediated effector responses |
| title_sort | 394 inclusion of cytomegalovirus viral fc gamma receptors in a glycoprotein b protein subunit vaccine improves fc mediated effector responses |
| url | https://www.cambridge.org/core/product/identifier/S2059866124010136/type/journal_article |
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