Efficient induction of comprehensive immune responses to control pathogenic E. coli by clay nano-adjuvant with the moderate size and surface charge

Weiyu Chen,Huali Zuo,Zhi Ping Xu,Bing Zhang,Barbara Rolfe,Timothy J. Mahony

doi:10.1038/s41598-017-13570-2

Abstract

In recent decades, diseases caused by pathogenic Escherichia coli (E. coli), enterohaemorrhagic E. coli (EHEC) O26 have been increasingly reported worldwide, which are as severe as those caused by EHEC strain O157:H7 and require effective intervention strategies. Herein, we report the application of clay nanoparticles, i.e. hectorites as effective nano-adjuvants for vaccination against EHEC O26 colonization. We show that medium size HEC (hectorite, around 73~77 nm diameter) is able to induce efficient humoral and cellular immune responses against EHEC antigen - intimin β (IB), which are significantly higher than those triggered by commercially used adjuvants - QuilA and Alum. We also demonstrate that mice immunized with IB adjuvanted with HEC nanoparticles elicit sufficient secretion of mucosal IgA, capable of providing effective protection against EHEC O26 binding to ruminant and human cells. In addition, we demonstrate for the first time that hectorites are able to initiate maturation of RAW 264.7 macrophages, inducing expression of co-stimulatory cytokines at a low nanoparticle concentration (10 μg/mL). Together these data strongly suggest that hectorite with optimized size is a highly efficient vaccine nano-adjuvant.

Highlights

The majority of E. coli are innocuous to human, enterohaemorrhagic E. coli (EHEC) strains are responsible for a broad-spectrum of diseases, including mild diarrhoea, haemorrhagic colitis and haemolytic uraemic syndrome[1,2]
EHEC O26 is capable of causing severe diseases including haemolytic uremic syndrome (HUS), which are normally triggered by EHEC O15711
Our results demonstrate that hectorite nanoparticles with the medium size and surface charge elicit strong cellular and humoral responses to IB, which are more valid than those induced by commercial adjuvants (Alum and QuilA) and more effectively protect host cells from invasion by EHEC O26

Summary

Introduction

The majority of E. coli are innocuous to human, EHEC strains are responsible for a broad-spectrum of diseases, including mild diarrhoea, haemorrhagic colitis and haemolytic uraemic syndrome[1,2]. Through generation of attaching and effacing (A/E) lesion and verotoxins[4], EHEC strains can trigger series of diseases in potential hosts and cause food poisoning outbreaks globally with varying severity depending on the virulence properties of the strain involved[5,6]. The application of an effective vaccine could significantly reduce the emergence of the increasing number of antimicrobial resistant diarrheagenic Escherichia coli generated by the indiscriminate use of antibiotics, the most common therapy against bacterial infections[22]. Side effects could result from vaccination in both human and animal, such as induced hemolytic activity and local inflammation at the injection site[23,24]. Even the FDA-approved and widely used adjuvant, Alum, has undesirable drawbacks, including local inflammation and preferential Th2-biased immune response and non-biodegradability, i.e. the adjuvant persists at the site of injection for more than one year[25,26]

Methods

Results

Conclusion