Epigallocatechin-3-Gallate as a Novel Vaccine Adjuvant.

Yucheol Cheong,Ji Eun Yu,Sanguine Byun,Jongkwan Lim,Hana Oh,Minjin Kim,Seung Won Yang,Jina Ahn,Min Seok Kim,Baik Lin Seong,Yo Han Jang,Wonil Chae

doi:10.3389/fimmu.2021.769088

Yucheol Cheong, Ji Eun Yu + Show 10 more

Open Access

https://doi.org/10.3389/fimmu.2021.769088

Copy DOI

Abstract

Vaccine adjuvants from natural resources have been utilized for enhancing vaccine efficacy against infectious diseases. This study examined the potential use of catechins, polyphenolic materials derived from green tea, as adjuvants for subunit and inactivated vaccines. Previously, catechins have been documented to have irreversible virucidal function, with the possible applicability in the inactivated viral vaccine platform. In a mouse model, the coadministration of epigallocatechin-3-gallate (EGCG) with influenza hemagglutinin (HA) antigens induced high levels of neutralizing antibodies, comparable to that induced by alum, providing complete protection against the lethal challenge. Adjuvant effects were observed for all types of HA antigens, including recombinant full-length HA and HA1 globular domain, and egg-derived inactivated split influenza vaccines. The combination of alum and EGCG further increased neutralizing (NT) antibody titers with the corresponding hemagglutination inhibition (HI) titers, demonstrating a dose-sparing effect. Remarkably, EGCG induced immunoglobulin isotype switching from IgG1 to IgG2a (approximately >64–700 fold increase), exerting a more balanced TH1/TH2 response compared to alum. The upregulation of IgG2a correlated with significant enhancement of antibody-dependent cellular cytotoxicity (ADCC) function (approximately 14 fold increase), providing a potent effector-mediated protection in addition to NT and HI. As the first report on a novel class of vaccine adjuvants with built-in virucidal activities, the results of this study will help improve the efficacy and safety of vaccines for pandemic preparedness.

Highlights

Classical vaccines composed of whole virions or bacteria, such as live attenuated or inactivated vaccines, have inherent immune-stimulating effects exerted by various components, including proteins, lipids, and nucleic acids
Viral HA inhibitory antibodies were considerably increased by the use of alum, Green tea extract (GT), or EGCG compared with non-adjuvanted HA (Figure 1D)
Alum and GT resulted in similar levels of PRNT50 neutralizing antibody titers; EGCG led to a moderate increase in neutralizing antibodies compared to non-adjuvanted HA (Figure 1E)

Summary

Introduction

Classical vaccines composed of whole virions or bacteria, such as live attenuated or inactivated vaccines, have inherent immune-stimulating effects exerted by various components, including proteins, lipids, and nucleic acids. New generation vaccine platforms such as subunit vaccines or nucleic acid (e.g. DNA) vaccines are relatively less immunogenic and, require. Since most vaccines are used in healthy people for prophylactic purposes, both vaccines and adjuvants are required to demonstrate a high level of safety and tolerability. Licensed or tested adjuvants can be classified into two groups: 1) immunomodulatory molecules that directly activate innate immune receptors including Toll-like receptors (TLRs), such as poly(I:C) and monophosphoryl lipid (MPL), and 2) particulate formulation systems that promote antigen delivery and uptake, such as aluminum salts, MF59, and liposomes [6]. AS adjuvant series such as AS01, AS03, and AS04 are currently used in human vaccines for various infectious diseases, such as influenza, herpes zoster, and hepatitis B virus [7,8,9]

Methods

Results

Conclusion