IgA binds to the AD-2 epitope of glycoprotein B and neutralizes human cytomegalovirus
Human cytomegalovirus (HCMV) is a ubiquitous pathogen that is potentially pathogenic in immunosuppressed individuals and pregnant females during primary infection. The HCMV envelope glycoprotein B (gB) facilitates viral entry into all cell types and induces a potent immune response. AD-2 epitope is...
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| Format: | Article |
| Language: | English |
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Wiley
2020
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| Online Access: | https://repository.londonmet.ac.uk/6240/1/Immunology_2020.pdf |
| _version_ | 1804072582579748864 |
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| author | Siddiqui, Saima Hackl, Sarah Ghoddusi, Hamid McIntosh, Megan Gomes, Ariane Ho, Joshua Reeves, Matthew B. McLean, Gary R. |
| author_facet | Siddiqui, Saima Hackl, Sarah Ghoddusi, Hamid McIntosh, Megan Gomes, Ariane Ho, Joshua Reeves, Matthew B. McLean, Gary R. |
| author_sort | Siddiqui, Saima |
| collection | LMU |
| description | Human cytomegalovirus (HCMV) is a ubiquitous pathogen that is potentially pathogenic in immunosuppressed individuals and pregnant females during primary infection. The HCMV envelope glycoprotein B (gB) facilitates viral entry into all cell types and induces a potent immune response. AD-2 epitope is a highly conserved linear neutralising epitope of gB and a critical target for antibodies, however, only 50% of seropositive individuals make IgG antibodies to this site and IgA responses have not been fully investigated. This study aimed to compare IgG and IgA responses against gB and the AD-2 epitope in naturally exposed individuals and those receiving a recombinant gB/MF59 adjuvant vaccine. Thus, vaccination of seropositive individuals improved pre-existing gB specific IgA and IgG levels and induced de novo gB specific IgA and IgG responses in seronegative recipients. Pre-existing AD-2 IgG and IgA responses were boosted with vaccination but de novo synthesis wasAD-2 responses were not detected. Naturally exposed individuals had dominant IgG responses towards gB and AD-2 compared with weaker and variable IgA responses, although a significant IgA binding response to AD-2 was observed within human breast milk samples. All antibodies binding AD-2 contained kappa light chains whereas balanced kappa/lambda light chain usage was found for those binding to gB. V-region matched AD-2 specific recombinant IgG and IgA bound both to gB and AD-2 and neutralized HCMV infection in vitro. Overall, these results indicate that although human IgG responses dominate, IgA class antibodies against AD-2 are a significant component of human milk which may function to protect neonates from HCMV. |
| first_indexed | 2024-07-09T04:01:26Z |
| format | Article |
| id | oai:repository.londonmet.ac.uk:6240 |
| institution | London Metropolitan University |
| language | English |
| last_indexed | 2024-07-09T04:01:26Z |
| publishDate | 2020 |
| publisher | Wiley |
| record_format | eprints |
| spelling | oai:repository.londonmet.ac.uk:62402023-06-30T14:04:23Z http://repository.londonmet.ac.uk/6240/ IgA binds to the AD-2 epitope of glycoprotein B and neutralizes human cytomegalovirus Siddiqui, Saima Hackl, Sarah Ghoddusi, Hamid McIntosh, Megan Gomes, Ariane Ho, Joshua Reeves, Matthew B. McLean, Gary R. 570 Life sciences; biology Human cytomegalovirus (HCMV) is a ubiquitous pathogen that is potentially pathogenic in immunosuppressed individuals and pregnant females during primary infection. The HCMV envelope glycoprotein B (gB) facilitates viral entry into all cell types and induces a potent immune response. AD-2 epitope is a highly conserved linear neutralising epitope of gB and a critical target for antibodies, however, only 50% of seropositive individuals make IgG antibodies to this site and IgA responses have not been fully investigated. This study aimed to compare IgG and IgA responses against gB and the AD-2 epitope in naturally exposed individuals and those receiving a recombinant gB/MF59 adjuvant vaccine. Thus, vaccination of seropositive individuals improved pre-existing gB specific IgA and IgG levels and induced de novo gB specific IgA and IgG responses in seronegative recipients. Pre-existing AD-2 IgG and IgA responses were boosted with vaccination but de novo synthesis wasAD-2 responses were not detected. Naturally exposed individuals had dominant IgG responses towards gB and AD-2 compared with weaker and variable IgA responses, although a significant IgA binding response to AD-2 was observed within human breast milk samples. All antibodies binding AD-2 contained kappa light chains whereas balanced kappa/lambda light chain usage was found for those binding to gB. V-region matched AD-2 specific recombinant IgG and IgA bound both to gB and AD-2 and neutralized HCMV infection in vitro. Overall, these results indicate that although human IgG responses dominate, IgA class antibodies against AD-2 are a significant component of human milk which may function to protect neonates from HCMV. Wiley 2020-12-13 Article PeerReviewed text en cc_by_4 https://repository.londonmet.ac.uk/6240/1/Immunology_2020.pdf Siddiqui, Saima, Hackl, Sarah, Ghoddusi, Hamid, McIntosh, Megan, Gomes, Ariane, Ho, Joshua, Reeves, Matthew B. and McLean, Gary R. (2020) IgA binds to the AD-2 epitope of glycoprotein B and neutralizes human cytomegalovirus. Immunology, 162 (3). pp. 314-327. ISSN 0019-2805 https://doi.org/10.1111/imm.13286 10.1111/imm.13286 |
| spellingShingle | 570 Life sciences; biology Siddiqui, Saima Hackl, Sarah Ghoddusi, Hamid McIntosh, Megan Gomes, Ariane Ho, Joshua Reeves, Matthew B. McLean, Gary R. IgA binds to the AD-2 epitope of glycoprotein B and neutralizes human cytomegalovirus |
| title | IgA binds to the AD-2 epitope of glycoprotein B and neutralizes human cytomegalovirus |
| title_full | IgA binds to the AD-2 epitope of glycoprotein B and neutralizes human cytomegalovirus |
| title_fullStr | IgA binds to the AD-2 epitope of glycoprotein B and neutralizes human cytomegalovirus |
| title_full_unstemmed | IgA binds to the AD-2 epitope of glycoprotein B and neutralizes human cytomegalovirus |
| title_short | IgA binds to the AD-2 epitope of glycoprotein B and neutralizes human cytomegalovirus |
| title_sort | iga binds to the ad 2 epitope of glycoprotein b and neutralizes human cytomegalovirus |
| topic | 570 Life sciences; biology |
| url | https://repository.londonmet.ac.uk/6240/1/Immunology_2020.pdf |
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