Restoration of viral epithelial tropism improves immunogenicity in rabbits and rhesus macaques for a whole virion vaccine of human cytomegalovirus
| Autor: | Adam C. Finnefrock, Tong-Ming Fu, Sheri Dubey, Dai Wang, Suzanne Cole, Jan ter Meulen, Xi He, Daniel C. Freed, Danilo R. Casimiro, Aimin Tang, Fengsheng Li, John W. Shiver |
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| Rok vydání: | 2012 |
| Předmět: |
Human cytomegalovirus
viruses Cytomegalovirus Antibodies Viral Virus Cytomegalovirus Vaccines Mice Viral Proteins Viral entry medicine Animals Neutralizing antibody Tropism Mice Inbred BALB C General Veterinary General Immunology and Microbiology biology Immunogenicity Public Health Environmental and Occupational Health Epithelial Cells medicine.disease Antibodies Neutralizing Macaca mulatta Virology Vaccination Viral Tropism Infectious Diseases Immunology biology.protein Molecular Medicine Female Rabbits Antibody |
| Zdroj: | Vaccine. 30:7469-7474 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2012.10.053 |
| Popis: | Maternal immunity to human cytomegalovirus (HCMV) prior to conception is ~70% protective against congenital transmission and in utero infection of HCMV. Both functional antibodies capable of neutralizing virus and effective T-cells are believed to be important for the protection. Previous HCMV vaccines have rarely been shown able to induce neutralizing antibody titers comparable to those seen in naturally infected HCMV seropositive subjects. Recent studies link a glycoprotein H (gH) complex to receptor-mediated viral entry of endothelial/epithelial cells and leukocytes. This pentameric gH complex, composed of five proteins (gH, gL, UL128, UL130 and UL131 proteins), is notably missing in all HCMV vaccine previously evaluated in clinic. Here we showed that a HCMV virus, with restored expression of the pentameric gH complex, can induce 10-fold higher neutralizing antibody titers than an attenuated AD169 virus or a recombinant glycoprotein B vaccine in multiple animal species in which viral replication is not expected. Encouragingly, the peak neutralizing titers post vaccination in rabbits and monkeys were within 2-4-fold of the levels determined in HCMV seropositive subjects. Functional antibodies by vaccination could further be improved when formulated with a novel adjuvant, and the titers of the antiviral antibodies were sustained in rabbits for over a year after vaccination. These results indicate that the pentameric gH complex is associated with greatly improved functional antibodies following vaccination, and support a vaccine concept based on a nonreplicating whole HCMV with the pentameric gH-associated epithelial tropism restored. |
| Databáze: | OpenAIRE |
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