Neutralization of Diverse Human Cytomegalovirus Strains Conferred by Antibodies Targeting Viral gH/gL/pUL128-131 Pentameric Complex
| Autor: | Aimin Tang, Melissa Hamm, Hua Zhu, Josef Vlasak, Dai Wang, Michael A. McVoy, John W. Loughney, Pete A. DePhillips, Ningyan Zhang, Matthew C. Troutman, Daniel C. Freed, Jason S. McLellan, Stuart P. Adler, Sha Ha, Zhiqiang An, Fengsheng Li, Tong-Ming Fu, David C. Nickle, Richard R. Rustandi, I-Ming Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Hyperimmune globulin Human cytomegalovirus Immunology Congenital cytomegalovirus infection Cytomegalovirus Antibodies Viral Microbiology Virus Cell Line 03 medical and health sciences strain coverage Viral Envelope Proteins Immunity Antibody Specificity Virology Vaccines and Antiviral Agents medicine pentameric complex antibodies Animals Humans biology Viral Vaccine Vaccination Viral Vaccines neutralization vaccines Virus Internalization medicine.disease Antibodies Neutralizing Macaca mulatta epitope mapping 030104 developmental biology human cytomegalovirus Insect Science Cytomegalovirus Infections biology.protein Rabbits Antibody Protein Binding |
| Zdroj: | Journal of Virology |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross-neutralize the field strains of HCMV, remains a challenge. In this study, with a panel of neutralizing antibodies from three healthy human donors with natural HCMV infection or a vaccinated animal, we mapped eight sites on the dominant virus-neutralizing antigen—the pentameric complex of glycoprotein H (gH), gL, and pUL128, pUL130, and pUL131. By evaluating the site-specific antibodies in vaccine immune sera, we demonstrated that vaccination elicited functional antiviral antibodies to multiple neutralizing sites in rhesus macaques, with quality attributes comparable to those of CMV hyperimmune globulin. Furthermore, these immune sera showed antiviral activities against a panel of genetically distinct HCMV clinical isolates. These results highlighted the importance of understanding the quality of vaccine-induced antibody responses, which includes not only the neutralizing potency in key cell types but also the ability to protect against the genetically diverse field strains. IMPORTANCE HCMV is the leading cause of congenital viral infection, and development of a preventive vaccine is a high public health priority. To understand the strain coverage of vaccine-induced immune responses in comparison with natural immunity, we used a panel of broadly neutralizing antibodies to identify the immunogenic sites of a dominant viral antigen—the pentameric complex. We further demonstrated that following vaccination of a replication-defective virus with the restored pentameric complex, rhesus macaques can develop broadly neutralizing antibodies targeting multiple immunogenic sites of the pentameric complex. Such analyses of site-specific antibody responses are imperative to our assessment of the quality of vaccine-induced immunity in clinical studies. |
| Databáze: | OpenAIRE |
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