Human Cytomegalovirus Vaccine Based on the Envelope gH/gL Pentamer Complex

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Human cytomegalovirus (HCMV) fetal infection during pregnancy and infection of immunocompromised patients are both clinical problems considered extremely important by the Institute of Medicine. Limited efficacy against primary HCMV infection was found using a subunit vaccine based on glycoprotein B, an important neutralizing antibody determinant blocking HCMV entry into fibroblasts. The HCMV field has been transformed by the discovery that a five-member (pentamer) protein complex is a required factor for epithelial and endothelial cell entry and indispensable for transmission as shown in non-human primates. Targeting HCMV with antibodies specific to the pentamer may interrupt horizontal and vertical transmission. We describe an innovative vaccine strategy to induce serum neutralizing antibodies of impressive magnitude against HCMV in two animal models. Using an attenuated poxvirus vector system, we demonstrate that co-expression of all five pentamer components is significantly more potent to induce serum neutralizing antibodies than subunit subsets of the complex or glycoprotein B, reaching peak levels comparable to HCMV hyperimmune globulin. A vaccine that elicits systemic and mucosal antibody responses that prevents infection of multiple cell types crucial to natural history of HCMV infection could play a role in preventing congenital HCMV infection and control of infection in immunocompromised patients.

Vyšlo v časopise: Human Cytomegalovirus Vaccine Based on the Envelope gH/gL Pentamer Complex. PLoS Pathog 10(11): e32767. doi:10.1371/journal.ppat.1004524
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004524

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