Development of lactococcal GEM-based pneumococcal vaccines

Sandrine A. L. Audouy; Saskia van Selm; Maarten L. van Roosmalen; Eduard Post; Rolf Kanninga; Jolanda Neef; Silvia Estevao; Edward E. S. Nieuwenhuis; Peter V. Adrian; Kees Leenhouts; Peter W. M. Hermans

doi:10.1016/j.vaccine.2006.09.026

Development of lactococcal GEM-based pneumococcal vaccines

Sandrine A. L. Audouy
, Saskia van Selm
, Maarten L. van Roosmalen
, Eduard Post
, Rolf Kanninga
, Jolanda Neef
, Silvia Estevao
, Edward E. S. Nieuwenhuis
, Peter V. Adrian
, Kees Leenhouts
, Peter W. M. Hermans^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

100 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	2497-2506
Number of pages	10
Journal	Vaccine
Volume	25
Issue number	13
DOIs	https://doi.org/10.1016/j.vaccine.2006.09.026
Publication status	Published - 22-Mar-2007
Event	5th International Symposium on Pneumococci and Pneumococcal Diseases - , Australia Duration: 2-Apr-2006 → 6-Apr-2006

Keywords

nasal vaccine
Streptococcus pneumoniae
Gram-positive Enhancer Matrix (GEM)
LACTIC-ACID BACTERIA
SURFACE PROTEIN-A
TOXIN FRAGMENT-C
POLYSACCHARIDE CONJUGATE VACCINES
CELLULAR IMMUNE-RESPONSES
GRAM-NEGATIVE BACTERIA
NECROSIS-FACTOR-ALPHA
STREPTOCOCCUS-PNEUMONIAE
INTRANASAL IMMUNIZATION
TETANUS TOXIN

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title = "Development of lactococcal GEM-based pneumococcal vaccines",

abstract = "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.",

keywords = "nasal vaccine, Streptococcus pneumoniae, Gram-positive Enhancer Matrix (GEM), LACTIC-ACID BACTERIA, SURFACE PROTEIN-A, TOXIN FRAGMENT-C, POLYSACCHARIDE CONJUGATE VACCINES, CELLULAR IMMUNE-RESPONSES, GRAM-NEGATIVE BACTERIA, NECROSIS-FACTOR-ALPHA, STREPTOCOCCUS-PNEUMONIAE, INTRANASAL IMMUNIZATION, TETANUS TOXIN",

author = "Audouy, \{Sandrine A. L.\} and \{van Selm\}, Saskia and \{van Roosmalen\}, \{Maarten L.\} and Eduard Post and Rolf Kanninga and Jolanda Neef and Silvia Estevao and Nieuwenhuis, \{Edward E. S.\} and Adrian, \{Peter V.\} and Kees Leenhouts and Hermans, \{Peter W. M.\}",

year = "2007",

month = mar,

day = "22",

doi = "10.1016/j.vaccine.2006.09.026",

language = "English",

volume = "25",

pages = "2497--2506",

journal = "Vaccine",

issn = "0264-410X",

publisher = "ELSEVIER SCI LTD",

number = "13",

note = "5th International Symposium on Pneumococci and Pneumococcal Diseases ; Conference date: 02-04-2006 Through 06-04-2006",

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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

SN - 0264-410X

VL - 25

SP - 2497

EP - 2506

JO - Vaccine

JF - Vaccine

IS - 13

T2 - 5th International Symposium on Pneumococci and Pneumococcal Diseases

Y2 - 2 April 2006 through 6 April 2006

ER -

Development of lactococcal GEM-based pneumococcal vaccines

Abstract

Keywords

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