TY - JOUR
T1 - Development of lactococcal GEM-based pneumococcal vaccines
AU - Audouy, Sandrine A. L.
AU - van Selm, Saskia
AU - van Roosmalen, Maarten L.
AU - Post, Eduard
AU - Kanninga, Rolf
AU - Neef, Jolanda
AU - Estevao, Silvia
AU - Nieuwenhuis, Edward E. S.
AU - Adrian, Peter V.
AU - Leenhouts, Kees
AU - Hermans, Peter W. M.
PY - 2007/3/22
Y1 - 2007/3/22
N2 - We report the development of a novel protein-based nasal vaccine against Streptococcus pneumoniae, in which three pneumococcal proteins were displayed on the surface of a non-recombinant, killed Lactococcus lactis-derived delivery system, called Gram-positive Enhancer Matrix (GEM). The GEM particles induced the production of the proinflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) by macrophages as well as the maturation of dendritic cells. The pneumococcal proteins IgA1 protease (IgA1p), putative proteinase maturation protein A (PpmA) and streptococcal lipoprotein A (SlrA) were anchored in trans to the surface of the GEM particles after recombinant production of the antigens in L. lactis as hybrids with a lactococcal cell wall binding domain, named Protein Anchor domain (PA). Intranasal immunisation with the SlrA-IgAlp or trivalent vaccine combinations without additional adjuvants showed significant protection against fatal pneumococcal pneumonia in mice. The GEM-based trivalent vaccine is a potential pneumococcal vaccine candidate that is expected to be easy to administer, safe and affordable to produce. (C) 2006 Elsevier Ltd. All rights reserved.
AB - We report the development of a novel protein-based nasal vaccine against Streptococcus pneumoniae, in which three pneumococcal proteins were displayed on the surface of a non-recombinant, killed Lactococcus lactis-derived delivery system, called Gram-positive Enhancer Matrix (GEM). The GEM particles induced the production of the proinflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) by macrophages as well as the maturation of dendritic cells. The pneumococcal proteins IgA1 protease (IgA1p), putative proteinase maturation protein A (PpmA) and streptococcal lipoprotein A (SlrA) were anchored in trans to the surface of the GEM particles after recombinant production of the antigens in L. lactis as hybrids with a lactococcal cell wall binding domain, named Protein Anchor domain (PA). Intranasal immunisation with the SlrA-IgAlp or trivalent vaccine combinations without additional adjuvants showed significant protection against fatal pneumococcal pneumonia in mice. The GEM-based trivalent vaccine is a potential pneumococcal vaccine candidate that is expected to be easy to administer, safe and affordable to produce. (C) 2006 Elsevier Ltd. All rights reserved.
KW - nasal vaccine
KW - Streptococcus pneumoniae
KW - Gram-positive Enhancer Matrix (GEM)
KW - LACTIC-ACID BACTERIA
KW - SURFACE PROTEIN-A
KW - TOXIN FRAGMENT-C
KW - POLYSACCHARIDE CONJUGATE VACCINES
KW - CELLULAR IMMUNE-RESPONSES
KW - GRAM-NEGATIVE BACTERIA
KW - NECROSIS-FACTOR-ALPHA
KW - STREPTOCOCCUS-PNEUMONIAE
KW - INTRANASAL IMMUNIZATION
KW - TETANUS TOXIN
U2 - 10.1016/j.vaccine.2006.09.026
DO - 10.1016/j.vaccine.2006.09.026
M3 - Article
VL - 25
SP - 2497
EP - 2506
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 13
T2 - 5th International Symposium on Pneumococci and Pneumococcal Diseases
Y2 - 2 April 2006 through 6 April 2006
ER -