Polymeric Caffeic Acid Acts as a Nasal Vaccine Formulation against Streptococcus pneumoniae Infections in Mice.

Rui Tada,Yoichi Negishi,Yoshiyuki Adachi,Daisuke Yamanaka,Jun Kunisawa,Hidehiko Suzuki,Miki Ogasawara

doi:10.3390/pharmaceutics13040585

Abstract

Infectious diseases are the second leading cause of death worldwide, highlighting the importance of the development of a novel and improved strategy for fighting pathogenic microbes. Streptococcus pneumoniae is a highly pathogenic bacteria that causes pneumonia with high mortality rates, especially in children and elderly individuals. To solve these issues, a mucosal vaccine system would be the best solution for the prevention and treatment of these diseases. We have recently reported that enzymatically polymerized caffeic acid (pCA) acts as a mucosal adjuvant when co-administered with antigenic proteins via the nasal route. Moreover, the sources of caffeic acid and horseradish peroxidase are ingredients found commonly in coffee beans and horseradish, respectively. In this study, we aimed to develop a pneumococcal nasal vaccine comprising pneumococcal surface protein A (PspA) and pCA as the mucosal adjuvant. Intranasal immunization with PspA and pCA induced the production of PspA-specific antibody responses in the mucosal and systemic compartments. Furthermore, the protective effects were tested in a murine model of S. pneumoniae infection. Intranasal vaccination conferred antigen-dependent protective immunity against a lethal infection of S. pneumoniae. In conclusion, pCA is useful as a serotype-independent universal nasal pneumococcal vaccine formulation.

Highlights

There have been substantial advances in modern medicine, infectious diseases are the second leading cause of death worldwide [1]
We examined whether the combined intranasal administration of polymerized caffeic acid (pCA) and pneumococcal surface protein A (PspA), a well-known pneumococcal antigen expressed in all pneumococcal strains, enhanced PspA-specific antibody production in the mucosal and systemic compartments
Intranasal vaccination with phosphate-buffered saline (PBS) or PspA alone did not result in PspA-specific IgA and IgG production in the nasal, lung, and vaginal compartments under the same experimental conditions

Summary

Introduction

There have been substantial advances in modern medicine, infectious diseases are the second leading cause of death worldwide [1]. There is an urgent need to develop novel drugs or strategies for the prevention and treatment of infectious diseases. For this purpose, vaccines are considered an important path to overcome infectious diseases and are being actively researched. There are only about 20 infectious diseases that can be prevented by a vaccine, termed vaccine-preventable diseases (VPD) [2]. Streptococcus pneumoniae is a highly pathogenic bacteria that causes pneumonia, meningitis, and septicemia with high mortality rates, especially in children and elderly individuals. The increase in the number of antibiotic-resistant S. pneumoniae strains has made the treatment and management of pneumococcal infections more challenging [3]

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