Injectable Elastin-Like Polypeptide Hydrogel Depot System for Assessment of the Immune-Response-Inducing Efficacy of Sustained Antigen Release Alone

35 Pages Posted: 9 Apr 2019

See all articles by Daisuke Asaia

Daisuke Asaia

St. Marianna University - Department of Microbiology

Tadashi Fukuda

National Institute of Infectious Diseases - Department of Bacteriology II

Kazunori Morokuma

KM Biologics Co., Ltd. - Quality Control Department

Daiki Funamoto

Kyushu University - Department of Applied Chemistry

Yuko Yamaguchi

KM Biologics Co., Ltd. - Quality Control Department

Takeshi Mori

Kyushu University - Department of Applied Chemistry

Yoshiki Katayama

Kyushu University - Department of Applied Chemistry; Chung Yuan Christian University - Department of Biomedical Engineering

Keigo Shibayama

National Institute of Infectious Diseases - Department of Bacteriology II

Hideki Nakashima

St. Marianna University - Department of Microbiology

Date Written: April 9, 2019

Abstract

Vaccines typically contain an antigen, delivery system (vehicle) and adjuvant, all of which contribute to the induction of a potent immune response. Consequently, design of new vaccines is difficult, because the contributions and interactions of these components are not easy to identify. Here, we aimed to develop an easy-to-use, immunologically inert, injectable depot system for sustained antigen release that would be suitable for assessing the efficacy of prolonged antigen exposure per se for inducing an immune response. This should mimic real-life infections. We selected recombinant elastin-like polypeptides with periodic cysteine residues (cELPs) as carriers and tetanus toxoid (Ttd) as an antigen. After subcutaneous injection of the mixture, cELP rapidly formed a disulfide cross-linked hydrogel in situ, within which Ttd is physically incorporated, affording a biodegradable antigen depot. We examined the stability and Ttd-release profile of a series of Ttd-containing hydrogels. A single injection induced high levels of tetanus antibody with high avidity for at least 20 weeks in mice. The chain length of cELP proved critical, whereas differences in hydrophobicity had little effect, although hydrophilic cELPs were more rapidly biodegraded. The ability of this system to separately identify the contribution of sustained antigen release to antibody induction should be helpful for rational design of next-generation vaccines.

Keywords: antigen depot, tetanus toxoid, antigen delivery, polypeptide, drug delivery

Suggested Citation

Asaia, Daisuke and Fukuda, Tadashi and Morokuma, Kazunori and Funamoto, Daiki and Yamaguchi, Yuko and Mori, Takeshi and Katayama, Yoshiki and Shibayama, Keigo and Nakashima, Hideki, Injectable Elastin-Like Polypeptide Hydrogel Depot System for Assessment of the Immune-Response-Inducing Efficacy of Sustained Antigen Release Alone (April 9, 2019). Available at SSRN: https://ssrn.com/abstract=3368800

Daisuke Asaia (Contact Author)

St. Marianna University - Department of Microbiology ( email )

Kawasaki
Japan

Tadashi Fukuda

National Institute of Infectious Diseases - Department of Bacteriology II

Japan

Kazunori Morokuma

KM Biologics Co., Ltd. - Quality Control Department

Kumamoto
Japan

Daiki Funamoto

Kyushu University - Department of Applied Chemistry

Japan

Yuko Yamaguchi

KM Biologics Co., Ltd. - Quality Control Department

Kumamoto
Japan

Takeshi Mori

Kyushu University - Department of Applied Chemistry

Japan

Yoshiki Katayama

Kyushu University - Department of Applied Chemistry

Japan

Chung Yuan Christian University - Department of Biomedical Engineering

Taiwan

Keigo Shibayama

National Institute of Infectious Diseases - Department of Bacteriology II

Japan

Hideki Nakashima

St. Marianna University - Department of Microbiology

Kawasaki
Japan

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