Mucosal Vaccine Made from Live, RecombinantLactococcus lactisProtects Mice against Pharyngeal Infection withStreptococcus pyogenes

Abstract

A novel vaccine (LL-CRR) made from live, nonpathogenic Lactococcus lactis that expresses the conserved C-repeat region (CRR) of M protein from Streptococcus pyogenes serotype 6 was tested in mice. Nasally vaccinated mice produced CRR-specific salivary immunoglobulin A (IgA) and serum IgG. Subcutaneously vaccinated mice produced CRR-specific serum IgG but not salivary IgA. A combined regimen produced responses similar to the salivary IgA of nasally vaccinated mice and serum IgG of subcutaneously vaccinated mice. Mice vaccinated nasally or with the combined regimen were significantly protected against pharyngeal infection following a nasal challenge with S. pyogenes M serotype 14. Mice vaccinated subcutaneously were not protected against pharyngeal infection. Mice in all three LL-CRR vaccination groups were significantly protected against the lethal effects of S. pyogenes. Only 1 of 77 challenged mice that were vaccinated with LL-CRR died, whereas 60 of 118 challenged mice that were vaccinated with a control strain or phosphatebuffered saline died. In conclusion, mucosal vaccination with LL-CRR produced CRR-specific salivary IgA and serum IgG, prevented pharyngeal infection with S. pyogenes, and promoted survival.

Expression of a Biologically Active GFP-αS1-Casein Fusion Protein in Lactococcus lactis

“…In particular, lactic acid bacteria such as Lc. lactis and certain species of lactobacilli possess a number of attractive properties that make them suitable candidates for the development of mucosal vaccines [10].…”

Lactococcus lactis GEM particles displaying pneumococcal antigens induce local and systemic immune responses following intranasal immunization

“…Because these recombi-nant LAB are suitable for mucosal immunization, they seem particularly useful for the development of vaccines against pathogens invading the body through the mucosal surface. This is illustrated by the recent work of Mannam et al in which L. lactis cells expressing part of the virulent factor M provided protection in nasally immunized mice against a lethal nasal challenge with Streptococcus pyogenes [18]. Although L. lactis and other LAB are safe bacteria, their widespread use as recombinant strains in mucosal vaccinations may cause unwanted horizontal gene transfer of the recombinant DNA to other (micro)organisms.…”

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

“…An alternative approach is to target the highly conserved C-repeat region of the M protein, as this eliminates concerns regarding serotype-specific antibody responses. Protection has been observed following heterologous expression of the C-repeat region by vaccinia virus (547) and Lactococcus lactis (548). Conformationally restricted C-repeat-region peptides (J8 and J14 and derivatives thereof and StreptInCor, a 55-mer peptide containing Band T-cell epitopes from the conserved region of the M5 protein) have been extensively studied and were observed to induce bactericidal and/or protective antibodies in animal-based trials (549)(550)(551)(552)(553)(554)(555)(556)(557)(558)(559)(560).…”