Bioengineered polyester beads co-displaying protein and carbohydrate-based antigens induce protective immunity against bacterial infection

Majela González-Miró,Laura M Rodríguez-Noda,Caridad Zayas-Vignier,Mabel Hernández-Cedeño,Vicente Vérez-Bencomo,Barbara Cedré-Marrero,Torsten Kleffmann,Sandra Madariaga-Zarza,Bernd H A Rehm,Mildrey Fariñas-Medina,Dagmar García-Rivera

doi:10.1038/s41598-018-20205-7

Majela González-Miró, Laura M Rodríguez-Noda + Show 9 more

Open Access

https://doi.org/10.1038/s41598-018-20205-7

Copy DOI

Abstract

The efficacy of protein and carbohydrate antigens as vaccines can be improved via particulate delivery strategies. Here, protein and carbohydrate antigens used in formulations of vaccines against Neisseria menigitidis were displayed on in vivo assembled polyester beads using a combined bioengineering and conjugation approach. An endotoxin-free mutant of Escherichia coli was engineered to produce translational fusions of antigens (Neisseria adhesin A (NadA) and factor H binding protein (fHbp) derived from serogroup B) to the polyhydroxybutyrate synthase (PhaC), in order to intracellularly assemble polyester beads displaying the respective antigens. Purified beads displaying NadA showed enhanced immunogenicity compared to soluble NadA. Both soluble and particulate NadA elicited functional antibodies with bactericidal activity associated with protective immunity. To expand the antigen repertoire and to design a more broadly protective vaccine, NadA-PhaC beads were additionally conjugated to the capsular polysaccharide from serogroup C. Co-delivery of surface displayed NadA and the capsular polysaccharide induced a strong and specific Th1/Th17 mediated immune response associated with functional bactericidal antibodies. Our findings provide the foundation for the design of multivalent antigen-coated polyester beads as suitable carriers for protein and polysaccharide antigens in order to induce protective immunity.

Highlights

There is a growing world-wide demand for efficient and broadly protective vaccines for the prevention of infectious diseases
Serogroup C is still responsible for many deaths[8] and serogroup B which causes more than half of the cases of the meningococcal disease world-wide, is not included in any conjugate vaccine as its capsular polysaccharides (CPS) is similar to polysaccharides presented in human neurologic tissues[9]
ClearcoliTM, an endotoxin-free mutant of E. coli, harbouring plasmid pMCS69 encoding PhaA and PhaB, which sequentially catalyze the synthesis of PHB precursors, was transformed with plasmids encoding PhaC fusion proteins (Supplementary Table 1)

Summary

Introduction

There is a growing world-wide demand for efficient and broadly protective vaccines for the prevention of infectious diseases. The WHO reported a global incidence of ~1.3 million cases per annum with a mortality of 5–15% and more than 25% of disabled survivors[2] The pathogenicity of this bacterium is based on virulence factors such as capsular polysaccharides (CPS), outer membranes proteins (adhesins and porins) and lipopolysaccharides. Serogroup C is still responsible for many deaths[8] and serogroup B which causes more than half of the cases of the meningococcal disease world-wide, is not included in any conjugate vaccine as its CPS is similar to polysaccharides presented in human neurologic tissues[9].

Objectives

Methods

Results

Discussion

Conclusion