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TitleAltered antigenicity and immunogenicity of human papillomavirus virus-like particles in the presence of thimerosal.
Journal, issue, pagesEur J Pharm Biopharm, Vol. 141, Page 221-231, Year 2019
Publish dateMay 30, 2019
AuthorsSiyi Chen / Xiaofen Huang / Yike Li / Xin Wang / Huirong Pan / Zhijie Lin / Qingbing Zheng / Shaowei Li / Jun Zhang / Ningshao Xia / Qinjian Zhao /
PubMed AbstractThimerosal has been widely used as a preservative in human vaccines for decades. Thimerosal, a thiol capping agent with ethyl mercury being the active degradant, could have impacts on the vaccine ...Thimerosal has been widely used as a preservative in human vaccines for decades. Thimerosal, a thiol capping agent with ethyl mercury being the active degradant, could have impacts on the vaccine potency due to potential thiol modification. The effects on the antigenicity and immunogenicity of human papillomavirus (HPV) virus-like particles (VLPs) in the presence of thimerosal was studied. In general, reduced binding activity was observed between HPV antigens and monoclonal antibodies (mAbs) upon thimerosal treatment, accompanied by reduced protein conformational stability. The immunogenicity of a pentavalent vaccine formulation (HPV6, HPV11, HPV16, HPV18 and hepatitis E virus) with or without thimerosal was studied in mice. The functional antibody titres, as well as the binding titres, were determined, showing a substantial decrease for vaccine formulations containing thimerosal for HPV16/18. Similarly, epitope-specific competition assays using specific and functional mAbs as tracers also showed a significant reduction in immunogenicity for HPV16/18 in the presence of thimerosal. Structural alterations in the capsid protein for HPV18 were observed with cryo-electron microscopy and 3-dimensional reconstruction in the comparative structural analysis. The results should alert scientists in formulation development field on the choice for vaccine preservatives, in particular for thiol-containing antigens.
External linksEur J Pharm Biopharm / PubMed:31154067
MethodsEM (single particle)
Resolution11.5 - 13.0 Å
Structure data

EMDB-9920:
The cryo-em structure of HPV18 VLP
Method: EM (single particle) / Resolution: 11.5 Å

EMDB-9921:
The cryo-em structure of Thimerosal-treated HPV18 VLP
Method: EM (single particle) / Resolution: 13.0 Å

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