Neutralization Epitopes in Trimer and Pentamer Complexes Recognized by Potent Cytomegalovirus-Neutralizing Human Monoclonal Antibodies

Yuanbao Ai, Changwen Wu, Ming Zhang, Dabbu Kumar Jaijyan, Tong Liu, Lipeng Zan, Nan Li, Wei Yu, Yueming Wang, Xiaohui Yuan, Chengming Li, Weihong Zheng, Hua Zhu, Hua Xin Liao

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Human cytomegalovirus (HCMV) infects 36% to almost 100% of adults and causes severe complications only in immunocompromised individuals. HCMV viral surface trimeric (gH/gL/gO) and pentameric (gH/gL/UL128/UL130/UL131A) complexes play important roles in HCMV infection and tropism. Here, we isolated and identified a total of four neutralizing monoclonal antibodies (MAbs) derived from HCMV-seropositive blood donors. Based on their reactivity to HCMV trimer and pentamer, these MAbs can be divided into two groups. MAbs PC0012, PC0014, and PC0035 in group 1 bind both trimer and pentamer and neutralize CMV by interfering with the postattachment steps of CMV entering into cells. These three antibodies recognize antigenic epitopes clustered in a similar area, which are overlapped by the epitope recognized by the known neutralizing antibody MSL-109. MAb PC0034 in group 2 binds only to pentamer and neutralizes CMV by blocking the binding of pentamer to cells. Epitope mapping using pentamer mutants showed that amino acid T94 of the subunit UL128 and K27 of UL131A on the pentamer are key epitope-associated residues recognized by PC0034. This study provides new evidence and insight information on the importance of the development of the CMV pentamer as a CMV vaccine. In addition, these newly identified potent CMV MAbs can be attractive candidates for development as antibody therapeutics for the prevention and treatment of HCMV infection.

Original languageEnglish (US)
JournalMicrobiology Spectrum
Volume10
Issue number6
DOIs
StatePublished - Nov 2022

All Science Journal Classification (ASJC) codes

  • Physiology
  • Ecology
  • General Immunology and Microbiology
  • Genetics
  • Microbiology (medical)
  • Cell Biology
  • Infectious Diseases

Keywords

  • gH/gL reactive
  • gH/gL/gO
  • human cytomegalovirus
  • neutralizing antibodies
  • pUL128/UL130/UL131A
  • pentamer complex
  • pentamer specific
  • therapeutics

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