Poly-γ-Glutamic Acid Complexed With Alum Induces Cross-Protective Immunity of Pandemic H1N1 Vaccine.

Quyen Thi Nguyen,Jaemoo Kim,Chaewon Kwak,Jinyoung Jeong,Wang Sik Lee,Moon Hee Sung,Jihyun Yang,Haryoung Poo

doi:10.3389/fimmu.2019.01604

Abstract

The use of a good vaccine adjuvant may induce a higher immunogenicity profile of vaccine antigens. Here, we developed a new adjuvant by combining poly-γ-glutamic acid (γ-PGA) with alum (PGA/Alum) and investigated its ability to enhance the immunogenicity and the cross-reactive efficacy of pandemic H1N1 (pH1N1) influenza vaccine antigen. PGA/Alum enhanced antigen delivery to draining lymph nodes and antigen-specific immunogenicity in mice using OVA as a model antigen. It also greatly increased OVA-specific antibody production, cytotoxic T lymphocyte (CTL) activity, and antibody-dependent cellular cytotoxicity (ADCC). These abilities of PGA/Alum improved the protective efficacy of pH1N1 vaccine antigen by increasing hemagglutination-inhibition titers, enhancing ADCC and CTL activity, and speeding viral clearance following homologous viral challenge. Importantly, the cross-protective efficacy of pH1N1 vaccine against heterologous viruses [A/Puerto Rico/8/34 (H1N1) and A/Hong Kong/1/1968 (H3N2)] was significantly enhanced by PGA/Alum, and cross-reactive ADCC and CTL activities were observed. Together, our results strongly suggest that PGA/Alum may be a promising vaccine adjuvant for preventing influenza and other infectious diseases.

Highlights

Traditional vaccines are composed of killed or attenuated viruses or bacteria and have several drawbacks, including safety concerns, the need for complicated culture of the infectious agents, and the low yields of their manufacturing processes [1, 2]
We evaluated the adjuvant efficacy of PGA/Alum in improving pandemic H1N1 influenza vaccine antigen-specific cellular immune responses, antibody (Ab) production, and crossreactivity against heterologous influenza A viruses
To develop a potential adjuvant for future clinical applications, we fabricated PGA/Alum by combining γ-PGA and alum, which is composed of aluminum hydroxide (AH) and magnesium hydroxide (MH)

Summary

Introduction

Traditional vaccines are composed of killed or attenuated viruses or bacteria and have several drawbacks, including safety concerns, the need for complicated culture of the infectious agents, and the low yields of their manufacturing processes [1, 2]. To solve these problems, researchers have developed new types of vaccine such as subunit recombinant vaccines and DNA vaccines [3]. Researchers have developed new types of vaccine such as subunit recombinant vaccines and DNA vaccines [3] Most of these vaccines are unable to generate sufficient antigen-specific immunogenicity to effectively prevent infectious diseases. The future development of effective influenza vaccines has been proposed to hinge on the use of adjuvants that improve the immunogenicity and cross-reactive immunity of vaccine antigens [5, 6].

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Results

Conclusion