IgA binds to the AD‐2 epitope of glycoprotein B and neutralizes human cytomegalovirus. Issue 3 (13th December 2020)

• Record Type: Journal Article
• Authors: Siddiqui, Saima; Hackl, Sarah; Ghoddusi, Hamid; McIntosh, Megan R.; Gomes, Ariane C.; Ho, Joshua; Reeves, Matthew B.; McLean, Gary R.
• Is Part Of: Immunology. Volume 162:Issue 3(2021)
• Page Start: 314
• Page End: 327
• Publication Date: 2020-12-13
• Subjects: AD‐2 epitope -- glycoprotein B -- human cytomegalovirus -- immunoglobulin A; Immunology -- Periodicals
• DOI: 10.1111/imm.13286
• Languages: English
• ISSNs: 0019-2805

Abstract

Summary: 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 neutralizing epitope of gB and a critical target for antibodies; however, only 50% of sero‐positive 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 sero‐positive individuals improved pre‐existing gB‐specific IgA and IgG levels and induced de novo gB‐specific IgA and IgG responses in sero‐negative recipients. Pre‐existing AD‐2 IgG and IgA responses were boosted with vaccination, but de novo AD‐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 breastmilk 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 to 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. Abstract : Human IgG and IgA responses to HCMV gB and AD‐2 epitope were determined. IgG to gB dominates, and a reduced frequency of AD‐2 responses, including IgA, is observed in serum and saliva, but IgA to AD‐2 dominates in human breastmilk. Vaccination studies demonstrated that IgA to gB could be induced but that IgA to AD‐2 was only induced in sero‐positive individuals.