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TitleRationally designed Human Cytomegalovirus gB nanoparticle vaccine with improved immunogenicity.
Journal, issue, pagesPLoS Pathog, Vol. 16, Issue 12, Page e1009169, Year 2020
Publish dateDec 28, 2020
AuthorsMichela Perotti / Jessica Marcandalli / Davide Demurtas / Federica Sallusto / Laurent Perez /
PubMed AbstractHuman cytomegalovirus (HCMV) is the primary viral cause of congenital birth defects and causes significant morbidity and mortality in immune-suppressed transplant recipients. Despite considerable ...Human cytomegalovirus (HCMV) is the primary viral cause of congenital birth defects and causes significant morbidity and mortality in immune-suppressed transplant recipients. Despite considerable efforts in vaccine development, HCMV infection still represents an unmet clinical need. In recent phase II trials, a MF59-adjuvanted gB vaccine showed only modest efficacy in preventing infection. These findings might be attributed to low level of antibodies (Abs) with a neutralizing activity induced by this vaccine. Here, we analyzed the immunogenicity of each gB antigenic domain (AD) and demonstrated that domain I of gB (AD5) is the main target of HCMV neutralizing antibodies. Furthermore, we designed, characterized and evaluated immunogenic responses to two different nanoparticles displaying a trimeric AD5 antigen. We showed that mice immunization with nanoparticles induces sera neutralization titers up to 100-fold higher compared to those obtained with the gB extracellular domain (gBECD). Collectively, these results illustrate with a medically relevant example the advantages of using a general approach combining antigen discovery, protein engineering and scaffold presentation for modern development of subunit vaccines against complex pathogens.
External linksPLoS Pathog / PubMed:33370407 / PubMed Central
MethodsEM (single particle)
Resolution19.0 - 20.0 Å
Structure data

EMDB-11398:
I5350 negative staining
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-11400:
Ferritin
Method: EM (single particle) / Resolution: 19.0 Å

Source
  • Homo sapiens (human)

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