| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Lanzavecchia, Antonio Marcandalli, Jessica Percivalle, Elena Preite, Silvia Gerna, Giuseppe Sallusto, Federica Kabanova, Anna Lilleri, Daniele Corti, Davide Perez, Laurent Becattini, Simone Fuschillo, Dario Agatic, Gloria |
| Description |
Author Affiliation: Kabanova A ( Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland); Perez L ( Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland); Lilleri D ( Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland); Marcandalli J ( Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland); Agatic G ( Humabs BioMed SA, 6500 Bellinzona, Switzerland); Becattini S ( Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland); Preite S ( Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland); Fuschillo D ( Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland); Percivalle E ( Virologia e Microbiologia, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, 27100 Pavia, Italy); Sallusto F ( Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland); Gerna G ( Laboratori Sperimentali di Ricerca and.); Corti D ( Humabs BioMed SA, 6500 Bellinzona, Switzerland); Lanzavecchia A ( Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland); |
| Abstract |
The use of neutralizing antibodies to identify the most effective antigen has been proposed as a strategy to design vaccines capable of eliciting protective B-cell immunity. In this study, we analyzed the human antibody response to cytomegalovirus (human cytomegalovirus, HCMV) infection and found that antibodies to glycoprotein (g)B, a surface glycoprotein that has been developed as a HCMV vaccine, were primarily nonneutralizing. In contrast, most of the antibodies to the complex formed by gH, gL, protein (p)UL128, pUL130, and pUL131 (the gHgLpUL128L pentamer) neutralized HCMV infection with high potency. Based on this analysis, we developed a single polycistronic vector encoding the five pentamer genes separated by 'self-cleaving' 2A peptides to generate a stably transfected CHO cell line constitutively secreting high levels of recombinant pentamer that displayed the functional antigenic sites targeted by human neutralizing antibodies. Immunization of mice with the pentamer formulated with different adjuvants elicited HCMV neutralizing antibody titers that persisted to high levels over time and that were a hundred- to thousand-fold higher than those found in individuals that recovered from primary HCMV infection. Sera from mice immunized with the pentamer vaccine neutralized infection of both epithelial cells and fibroblasts and prevented cell-to-cell spread and viral dissemination from endothelial cells to leukocytes. Neutralizing monoclonal antibodies from immunized mice showed the same potency as human antibodies and targeted the same as well as additional sites on the pentamer. These results illustrate with a relevant example a general and practical approach of analytic vaccinology for the development of subunit vaccines against complex pathogens. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
50 |
| Volume Number |
111 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2014-12-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Antibodies, Neutralizing Immunology Antigens, Viral Cytomegalovirus Vaccines Drug Design Animals Antibodies, Monoclonal Isolation & Purification CHO Cells Cricetinae Cricetulus Enzyme-Linked Immunosorbent Assay Genetic Vectors Genetics HEK293 Cells Mice Statistics, Nonparametric Vaccines, Subunit Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
