ArticleProceedings of the National Academy of Sciences of the United States of America2013
Pentameric complex of viral glycoprotein H is the primary target for potent neutralization by a human cytomegalovirus vaccine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 133 citations in OpenAlex.
- A Replication-Defective Human Cytomegalovirus Vaccine Elicits Humoral Immune Responses Analogous to Those with Natural Infection.Journal of virology · 2019Trial
- The Cellular Localization of Human Cytomegalovirus Glycoprotein Expression Greatly Influences the Frequency and Functional Phenotype of Specific CD4+ T Cell Responses.Journal of immunology (Baltimore, Md. : 1950) · 2015Trial
- A modular vaccine platform for optimized lipid nanoparticle mRNA immunogenicity.Nature biomedical engineering · 2026Article
- Progress and prospects for herpesvirus vaccination using gB antigens.Frontiers in immunology · 2026Review
- Replication-deficient whole-virus vaccines against cytomegalovirus induce protective immunity in a guinea pig congenital infection model.Journal of virology · 2025Article
- Human Cytomegalovirus Immune Evasion of Natural Killer Cells: A Virus for All Seasons?Pathogens (Basel, Switzerland) · 2025Review
- Small glycomimetic antagonists of the cytomegalovirus glycoprotein UL141 prevent binding to TRAIL death receptor.The Journal of biological chemistry · 2025Article
- Cytomegalovirus Genetic Diversity and Evolution: Insights into Genotypes and Their Role in Viral Pathogenesis.Pathogens (Basel, Switzerland) · 2025Review
- Activation of connexin hemichannels enhances mechanosensitivity and anabolism in disused and aged bone.JCI insight · 2024Article
- Fc gamma receptors promote antibody-induced LILRB4 internalization and immune regulation of monocytic AML.Antibody therapeutics · 2024Article
- Hematopoietic stem cell donor vaccination with cytomegalovirus triplex augments frequencies of functional and durable cytomegalovirus-specific T cells in the recipient: A novel strategy to limit antiviral prophylaxis.American journal of hematology · 2023Article
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- Development of broadly neutralizing antibodies targeting the cytomegalovirus subdominant antigen gH.Communications biology · 2022Article
- Cross Strain Protection against Cytomegalovirus Reduces DISC Vaccine Efficacy against CMV in the Guinea Pig Model.Viruses · 2022Article
- Identification of functionally important domains of human cytomegalovirus gO that act after trimer binding to receptors.PLoS pathogens · 2022Article
- Structural basis for HCMV Pentamer recognition by neuropilin 2 and neutralizing antibodies.Science advances · 2022Article
- Antibody Titers Against Human Cytomegalovirus gM/gN and gB Among Pregnant Women and Their Infants.Frontiers in pediatrics · 2022Article
- Dominant Antiviral CD8Frontiers in immunology · 2022Article
- Common Polymorphisms in the Glycoproteins of Human Cytomegalovirus and Associated Strain-Specific Immunity.Viruses · 2021Review
35 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human cytomegalovirus (HCMV) can cause serious morbidity/mortality in transplant patients, and congenital HCMV infection can lead to birth defects. Developing an effective HCMV vaccine is a high medical priority. One of the challenges to the efforts has been our limited understanding of the viral antigens important for protective antibodies. Receptor-mediated viral entry to endothelial/epithelial cells requires a glycoprotein H (gH) complex comprising five viral proteins (gH, gL, UL128, UL130, and UL131). This gH complex is notably missing from HCMV laboratory strains as well as HCMV vaccines previously evaluated in the clinic. To support a unique vaccine concept based on the pentameric gH complex, we established a panel of 45 monoclonal antibodies (mAbs) from a rabbit immunized with an experimental vaccine virus in which the expression of the pentameric gH complex was restored. Over one-half (25 of 45) of the mAbs have neutralizing activity. Interestingly, affinity for an antibody to bind virions was not correlated with its ability to neutralize the virus. Genetic analysis of the 45 mAbs based on their heavy- and light-chain sequences identified at least 26 B-cell linage groups characterized by distinct binding or neutralizing properties. Moreover, neutralizing antibodies possessed longer complementarity-determining region 3 for both heavy and light chains than those with no neutralizing activity. Importantly, potent neutralizing mAbs reacted to the pentameric gH complex but not to gB. Thus, the pentameric gH complex is the primary target for antiviral antibodies by vaccination.
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