Nanogel-based Pneumococcal Surface Protein A Nasal Vaccine Induces MicroRNA-associated Th17 Cell Responses with Neutralizing Antibodies Against Streptococcus Pneumoniae in Macaques

Overview

Journal Mucosal Immunol

Publisher Elsevier

Specialty Allergy & Immunology

Date 2015 Feb 12

PMID 25669148

Citations 31

Authors

Y Fukuyama

Y Yuki

Y Katakai

N Harada

H Takahashi

S Takeda

M Mejima

S Joo

S Kurokawa

S Sawada

H Shibata

E J Park

K Fujihashi

D E Briles

Y Yasutomi

H Tsukada

K Akiyoshi

H Kiyono

Affiliations

Soon will be listed here.

Abstract

We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [(18)F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [(18)F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans.

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