AddaVax Formulated with PolyI:C as a Potential Adjuvant of MDCK-based Influenza Vaccine Enhances Local, Cellular, and Antibody Protective Immune Response in Mice

Xuanxuan Nian,Tao Deng,Jiayou Zhang,Xiaoming Yang,Luyao Yao,Jing Liu,Shihe Huang,Junying Li,Zheng Gong,Chuanshuo Lv

doi:10.1208/s12249-021-02145-0

Xuanxuan Nian, Tao Deng + Show 8 more

Open Access

https://doi.org/10.1208/s12249-021-02145-0

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Abstract

Poor immune responses to inactivated influenza vaccine can be improved by effective and safe adjuvants to increase antibody titers and cellular protective response. In our study, AddaVax and PolyI:C combined adjuvant (AP adjuvant) were used for influenza vaccine development. After immunizing BALB/c mice and Wistar rats intramuscularly, Split inactivated H3N2 vaccine adjuvanted with AP elicited higher serum hemagglutination-inhibition antibodies and IgG titers. We demonstrated that AP induced a transient innate immune cytokines production at the injection site, induced H3N2 uptake by DCs, increased recruitment of monocytes and DCs in LNs, and promoted H3N2 vaccine migration; AP facilitated vaccines to induce a vigorous adaptive immune response. Besides, AP showed good safety as shown by lymph nodes (LNs) size, spleens index of BALB/c mice, and weight changes and C-reaction protein level of BALB/c mice and Wistar rats after repeated administration of high-dose vaccine with or without adjuvant. These findings indicate that AP is a potential novel adjuvant and can be used as a safe and effective adjuvant for MDCK-based influenza inactivated vaccine to induce cellular and antibody protective response.

Highlights

Seasonal influenza is a global public health threat, and vaccination is the most effective and dependable method for managing influenza epidemics [1]
Madin-Darby canine kidney (MDCK) cells are susceptible to influenza virus infection and support virus replication; they are used for cell-based influenza vaccines production [2]
Several adjuvants for influenza vaccine have been used in humans, and others are in the early stages of clinical studies

Summary

Introduction

Seasonal influenza is a global public health threat, and vaccination is the most effective and dependable method for managing influenza epidemics [1]. Madin-Darby canine kidney (MDCK) cells are susceptible to influenza virus infection and support virus replication; they are used for cell-based influenza vaccines production [2]. Most inactivated or subunit influenza vaccines are poorly immunogenic and are ineffective at producing high levels of vaccinespecific serum antibodies in humans. Adjuvants and delivery systems used to improve immunogenicity of vaccines must be safe and effective [3]. Several adjuvants for influenza vaccine have been used in humans, and others are in the early stages of clinical studies. Many adjuvants in the preclinical research stage present promising results[4]

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