Abstract

The successful development of a mucosal vaccine depends critically on the use of a safe and effective immunostimulant and/or carrier system. This review describes the effectiveness and mode of action of an immunostimulating particle, derived from bacteria, used in mucosal subunit vaccines. The non-living particles, designated bacterium-like particles are based on the food-grade bacterium Lactococcus lactis. The focus of the overview is on the development of intranasal BLP-based vaccines to prevent diseases caused by influenza and respiratory syncytial virus, and includes a selection of Phase I clinical data for the intranasal FluGEM vaccine.

Highlights

  • A key issue in the development of improved and new vaccines is safety, since most vaccines are given to healthy individuals

  • L. lactis is an innocuous Gram-positive bacterium that is commonly used in the food industry; it has Generally Recognized As Safe (GRAS) status of the Food and Drug Administration (FDA)

  • The procedure results in nonliving spherical shaped bacterium-like particles (BLPs) that have a diameter of approximately 1–2 μm and consist predominantly of a PGN outer surface (Figure 1)

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Summary

INTRODUCTION

A key issue in the development of improved and new vaccines is safety, since most vaccines are given to healthy individuals. In order to improve safety profiles, the use of well-defined (recombinant) purified antigens for the generation of subunit vaccines has become key in vaccine development programs. In order to minimize regulatory hurdles, we have developed a non-living particle that can be used as an immunostimulant for the improvement of existing vaccines and to enable mucosal application, or can be used as a vaccine carrier for subunit antigens. BLPs are used in two different formats They are used as an immunostimulant by mixing with vaccine antigens (admixed). The preferred format for use in recombinant subunit vaccines is a formulation in which the antigens are bound to the surface of BLPs. Binding of antigens to BLPs requires the presence of a PGN binding tag (Protan) in the antigen.

BLPs in mucosal subunit vaccine applications
Study outcome
Mouse Mouse Mouse
Infected mosquito challenge
MODE OF ACTION OF BLPs
BLPs INDUCE MATURATION AND ACTIVATION OF MOUSE AND HUMAN DCs
Mouse type
Findings
HI GMT ratio

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