ArticleProceedings of the National Academy of Sciences of the United States of America2014
Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 119 citations in OpenAlex.
- Cytomegalovirus immunity in high-risk liver transplant recipients following preemptive antiviral therapy versus prophylaxis.JCI insight · 2024Trial
- Cytomegalovirus Humoral Response Against Epithelial Cell Entry-Mediated Infection in the Primary Infection Setting After Hematopoietic Cell Transplantation.The Journal of infectious diseases · 2020Trial
- Antigenic-Specificity and Cytokine Profile of the T-Cell Response to Human Cytomegalovirus in Transplant Recipients.Pathogens (Basel, Switzerland) · 2026Article
- Progress and prospects for herpesvirus vaccination using gB antigens.Frontiers in immunology · 2026Review
- Human Cytomegalovirus Immune Evasion of Natural Killer Cells: A Virus for All Seasons?Pathogens (Basel, Switzerland) · 2025Review
- The pentameric complex is not required for congenital CMV transmission in seronegative rhesus macaques.Science translational medicine · 2025Article
- Complete cross strain protection against congenital cytomegalovirus infection requires a vaccine encoding key antibody (gB) and T-cell (immediate early 1 protein) viral antigens.Frontiers in immunology · 2025Article
- Different Antigen-Specific CD4Journal of clinical medicine · 2024Article
- Fibroblast, Epithelial and Endothelial Cell-Derived Human Cytomegalovirus Strains Display Distinct Neutralizing Antibody Responses and Varying Levels of gH/gL Complexes.International journal of molecular sciences · 2023Article
- Epstein-Barr virus gH/gL has multiple sites of vulnerability for virus neutralization and fusion inhibition.Immunity · 2022Article
- Horizontal Transmission of Cytomegalovirus in a Rhesus Model Despite High-Level, Vaccine-Elicited Neutralizing Antibody and T-Cell Responses.The Journal of infectious diseases · 2022Article
- Antibodies to combat viral infections: development strategies and progress.Nature reviews. Drug discovery · 2022Review
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- Article
- Development of broadly neutralizing antibodies targeting the cytomegalovirus subdominant antigen gH.Communications biology · 2022Article
- A Live Olfactory Mouse Cytomegalovirus Vaccine, Attenuated for Systemic Spread, Protects against Superinfection.Journal of virology · 2021Article
- A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial.NPJ vaccines · 2021Article
- Review
- A trimeric capable gB CMV vaccine provides limited protection against a highly cell associated and epithelial tropic strain of cytomegalovirus in guinea pigs.The Journal of general virology · 2021Article
- Monoclonal antibodies targeting nonstructural viral antigens can activate ADCC against human cytomegalovirus.The Journal of clinical investigation · 2021Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.