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Immune Responses to Varicella-Zoster Virus Glycoprotein E Formulated with Poly(Lactic-co-Glycolic Acid) Nanoparticles and Nucleic Acid Adjuvants in Mice

  • RESEARCH ARTICLE
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Virologica Sinica

Abstract

The subunit herpes zoster vaccine Shingrix is superior to attenuated vaccine Zostavax in both safety and efficacy, yet its unlyophilizable liposome delivery system and the limited supply of naturally sourced immunological adjuvant QS-21 still need to be improved. Based on poly(lactic-co-glycolic acid) (PLGA) delivery systems that are stable during the lyophilization and rehydration process and using a double-emulsion (w/o/w) solvent evaporation method, we designed a series of nanoparticles with varicella-zoster virus antigen glycoprotein E (VZV-gE) as an antigen and nucleic acids including polyinosinic-polycytidylic acid (Poly I:C) and phosphodiester CpG oligodeoxynucleotide (CpG ODN), encapsulated as immune stimulators. While cationic lipids (DOTAP) have more potential than neutral lipids (DOPC) for activating gE-specific cell-mediated immunity (CMI) in immunized mice, especially when gE is encapsulated in and presented on the surface of nanoparticles, PLGA particles without lipids have the greatest potential to induce not only the highest gE-specific IgG titers but also the strongest gE-specific CMI responses, including the highest proportions of interferon-γ (IFN-γ)- and interleukin-2 (IL-2)-producing CD4+/CD8+ T cells according to a flow cytometry assay and the greatest numbers of IFN-γ- and IL-2-producing splenocytes according to an enzyme-linked immunospot (ELISPOT) assay. These results showed that immune-stimulating nucleic acids together with the PLGA delivery system showed promise as a safe and economical varicella and zoster vaccine candidate.

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Acknowledgements

This work was financially supported by the CAMS Initiative for Innovative Medicine (Grant Number 2017-I2M-3-022), Central basic scientific research in colleges and universities (Grant Number 3332019162), the National Natural Science Foundation of China (Grant Number 81503117) and the Foundation for Studying Abroad from the China Scholarship Council (Grant Number 201808110121).

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  1. Yunfei Wang and Jialong Qi contributed equally to this work.

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  1. Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, 650118, China

    Yunfei Wang, Jialong Qi, Han Cao & Cunbao Liu

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  1. Yunfei Wang
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YW and JQ performed the experiments and analyzed the data. HC helped to perform part of the experiments. CL designed the study, drafted and finalized the manuscript.

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Correspondence to Cunbao Liu.

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Animal and Human Rights Statement

The animal experiments were approved by the Ethics Committee of Animal Care and Welfare of the Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College (Permit Number: SCXK (dian) K2017-0002), in accordance with the animal ethics guideline of the Chinese National Health and Medical Research Council and the Office of Laboratory Animal Management of Yunnan Province, China. All efforts were made to minimize animal suffering.

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Wang, Y., Qi, J., Cao, H. et al. Immune Responses to Varicella-Zoster Virus Glycoprotein E Formulated with Poly(Lactic-co-Glycolic Acid) Nanoparticles and Nucleic Acid Adjuvants in Mice. Virol. Sin. 36, 122–132 (2021). https://doi.org/10.1007/s12250-020-00261-y

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