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

96 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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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

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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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