Use of Lactococcus lactis expressing pili from group B Streptococcus as a broad-coverage vaccine against streptococcal disease.
Recent data indicate that the human pathogen group B Streptococcus (GBS) produces pilus-like structures encoded in genomic islands with similar organization to pathogenicity islands. On the basis of the amino acid sequence of their protein components, 3 different types of pili have been identified in GBS, at least 1 of which is present in all isolates. We recently demonstrated that recombinant pilus proteins protect mice from lethal challenge with GBS and are thus potential vaccine candidates. Here, we show that GBS pilin island 1, transferred into the nonpathogenic microorganism Lactococcus lactis, leads to pilus assembly. We also show that systemically or mucosally delivered Lactococcus expressing pilin island 1 protects mice from challenge with GBS isolates carrying pilus 1. Furthermore, lactococci engineered to express hybrid pili containing GBS pilus 1 and pilus 2 components confer protection against strains expressing either of the 2 pilus types. These data pave the way to the design of pilus-based, multivalent live vaccines against streptococcal pathogens.
Buccato
Scilla
S
Novartis Vaccines, 1 53100 Siena, Italy.
Maione
Domenico
D
Rinaudo
Cira Daniela
CD
Volpini
Gianfranco
G
Taddei
Anna Rita
AR
Rosini
Roberto
R
Telford
John L
JL
Grandi
Guido
G
Margarit
Immaculada
I
D000818:Animals; D005260:Female; D036781:Fimbriae Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000276:immunology; D044404:Genomic Islands; D013294:Lactococcus lactis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D013292:Streptococcus agalactiae / Q000235:genetics / Q000276:immunology*; D014169:Transformation, Bacterial / Q000235:genetics / Q000276:immunology
D011994:Recombinant Proteins; D022541:Streptococcal Vaccines; D036781:Fimbriae Proteins