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Abstract Title:

Altered antigenicity and immunogenicity of human papillomavirus virus-like particles in the presence of thimerosal.

Abstract Source:

Eur J Pharm Biopharm. 2019 May 30. Epub 2019 May 30. PMID: 31154067

Abstract Author(s):

Siyi Chen, Xiaofen Huang, Yike Li, Xin Wang, Huirong Pan, Zhijie Lin, Qingbing Zheng, Shaowei Li, Jun Zhang, Ningshao Xia, Qinjian Zhao

Article Affiliation:

Siyi Chen

Abstract:

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 proteins for HPV18 were observed with cryo-electron microscopy and 3-dimensional reconstruction in the comparative structural analysis. The results should alert scientists in formulations development field on the choice for vaccine preservatives, in particular for thiol-containing antigens.

Study Type : Animal Study
Additional Links
Anti Therapeutic Actions : Vaccination: All : CK(6351) : AC(662)
Problem Substances : Thimerosal : CK(618) : AC(151)

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Sayer Ji
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