A Fully Protective Congenital CMV Vaccine Requires Neutralizing Antibodies to Viral Pentamer and gB Glycoprotein Complexes but a pp65 T-Cell Response Is Not Necessary
| Autor: | Alistair McGregor, K. Yeon Choi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
gB T-Lymphocytes Guinea Pigs Congenital cytomegalovirus infection Roseolovirus Infections CMV vaccine Antibodies Viral Microbiology Virus Article pp65 gH Viral Matrix Proteins Viral Envelope Proteins Interferon Glycoprotein complex Immunity Viral entry Virology medicine Animals Humans neutralizing antibodies cytomegalovirus chemistry.chemical_classification glycoprotein complex biology Vaccination Viral Vaccines medicine.disease Antibodies Neutralizing QR1-502 congenital CMV Infectious Diseases chemistry Cytomegalovirus Infections biology.protein Female Antibody Glycoprotein Roseolovirus pentamer complex guinea pig medicine.drug |
| Zdroj: | Viruses, Vol 13, Iss 1467, p 1467 (2021) Viruses Volume 13 Issue 8 |
| ISSN: | 1999-4915 |
| Popis: | A vaccine against congenital cytomegalovirus infection is a high priority. Guinea pig cytomegalovirus (GPCMV) is the only congenital CMV small animal model. GPCMV encodes essential glycoprotein complexes for virus entry (gB, gH/gL/gO, gM/gN) including a pentamer complex (gH/gL/GP129/GP131/GP133 or PC) for endocytic cell entry. The cohorts for protection against congenital CMV are poorly defined. Neutralizing antibodies to the viral glycoprotein complexes are potentially more important than an immunodominant T-cell response to the pp65 protein. In GPCMV, GP83 (pp65 homolog) is an evasion factor, and the GP83 mutant GPCMV has increased sensitivity to type I interferon. Although GP83 induces a cell-mediated response, a GP83-only-based vaccine strategy has limited efficacy. GPCMV attenuation via GP83 null deletion mutant in glycoprotein PC positive or negative virus was evaluated as live-attenuated vaccine strains (GP83dPC+/PC-). Vaccinated animals induced antibodies to viral glycoprotein complexes, and PC+ vaccinated animals had sterilizing immunity against wtGPCMV challenge. In a pre-conception vaccine (GP83dPC+) study, dams challenged mid-2nd trimester with wtGPCMV had complete protection against congenital CMV infection without detectable virus in pups. An unvaccinated control group had 80% pup transmission rate. Overall, gB and PC antibodies are key for protection against congenital CMV infection, but a response to pp65 is not strictly necessary. |
| Databáze: | OpenAIRE |
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