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Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides lacking allergen-specific T cell epitopes reduces Bet v 1-specific T cell responses via blocking antibodies in a murine model for birch pollen allergy.

Linhart B, Narayanan M, Focke-Tejkl M, Wrba F, Vrtala S, Valenta R - Clin. Exp. Allergy (2014)

Bottom Line: The effects of peptide-specific and allergen-specific antibodies on T cell responses and allergic lung inflammation were studied using specific antibodies.Prophylactic and therapeutic vaccination of mice with the peptide vaccine induced Bet v 1-specific antibodies which suppressed Bet v 1-specific T cell responses and allergic lung inflammation.Vaccination with carrier-bound allergen-derived peptides lacking allergen-specific T cell epitopes induces allergen-specific IgG antibodies which suppress allergen-specific T cell responses and allergic lung inflammation.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

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Scheme for prophylactic and therapeutic vaccination with KLH-coupled peptides. Timelines of the prophylactic (P) and therapeutic (T) vaccination with peptides. Time points of sensitization (S) with Bet v 1, bleeding, and killing are indicated.
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fig02: Scheme for prophylactic and therapeutic vaccination with KLH-coupled peptides. Timelines of the prophylactic (P) and therapeutic (T) vaccination with peptides. Time points of sensitization (S) with Bet v 1, bleeding, and killing are indicated.

Mentions: Six-week-old female BALB/c mice were purchased from Charles River (Germany). Animals were maintained in the animal care unit of the Department of Pathophysiology and Allergy Research, Medical University of Vienna, according to the local guidelines for animal care. The study was approved by the local ethics committee. The mouse model of birch pollen allergy obtained by sensitization to the major birch pollen allergen, Bet v 1, was established similar as described 23. In all experiments, groups of 5 mice were investigated. In the prophylactic peptide vaccination protocol, mice were immunized subcutaneously (s.c.) with a mix containing 10 μg of each of the three KLH-coupled Bet v 1 peptides adsorbed to aluminium hydroxide three times in 3-week intervals according to the immunization scheme (Fig.2) and then sensitized s.c. with aluminium hydroxide-adsorbed Bet v 1 (10 μg) (i.e. group P+/S+). For control purposes, groups were included which received only prophylactic immunization, but no sensitization (i.e. group P+/S−), neither prophylactic immunization nor sensitization (i.e. group PBS) or only sensitization (i.e. group P−/S+). In the therapeutic scheme, mice were sensitized s.c. with Bet v 1 (10 μg) adsorbed to aluminium hydroxide (three injections in 3 weeks intervals) followed by three s.c. immunizations with the peptide vaccine (i.e. group S+/T+). For control purposes, mice were not sensitized but received the peptide vaccine (i.e. group S−/T+) or were only sensitized (i.e. group S+/T−). In total, 7 groups of mice were studied (groups PBS, P+/S−, P+/S+, P−/S+, S+/T+, S+/T− and S−/T+). Blood samples were taken from the tail vein one day before each immunization and 3 weeks after the last immunization and were stored at −20°C until analysis. Mice were killed at day 120 to obtain spleen cells. Results were obtained in two independent sets of experiments. In the second experiment, two groups of mice were included which received a prophylactic or a therapeutic immunization with an irrelevant, Bet v 1-unrelated (i.e. grass pollen allergen Phl p 5-derived peptide) peptide coupled to KLH. In addition, groups of mice (n = 5) underwent the same prophylactic and therapeutic immunization protocol using either wild-type Bet v 1, or Bet v 1 fragments or a Bet v 1 trimer (10 μg/mouse) 24,25 as vaccines.


Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides lacking allergen-specific T cell epitopes reduces Bet v 1-specific T cell responses via blocking antibodies in a murine model for birch pollen allergy.

Linhart B, Narayanan M, Focke-Tejkl M, Wrba F, Vrtala S, Valenta R - Clin. Exp. Allergy (2014)

Scheme for prophylactic and therapeutic vaccination with KLH-coupled peptides. Timelines of the prophylactic (P) and therapeutic (T) vaccination with peptides. Time points of sensitization (S) with Bet v 1, bleeding, and killing are indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215111&req=5

fig02: Scheme for prophylactic and therapeutic vaccination with KLH-coupled peptides. Timelines of the prophylactic (P) and therapeutic (T) vaccination with peptides. Time points of sensitization (S) with Bet v 1, bleeding, and killing are indicated.
Mentions: Six-week-old female BALB/c mice were purchased from Charles River (Germany). Animals were maintained in the animal care unit of the Department of Pathophysiology and Allergy Research, Medical University of Vienna, according to the local guidelines for animal care. The study was approved by the local ethics committee. The mouse model of birch pollen allergy obtained by sensitization to the major birch pollen allergen, Bet v 1, was established similar as described 23. In all experiments, groups of 5 mice were investigated. In the prophylactic peptide vaccination protocol, mice were immunized subcutaneously (s.c.) with a mix containing 10 μg of each of the three KLH-coupled Bet v 1 peptides adsorbed to aluminium hydroxide three times in 3-week intervals according to the immunization scheme (Fig.2) and then sensitized s.c. with aluminium hydroxide-adsorbed Bet v 1 (10 μg) (i.e. group P+/S+). For control purposes, groups were included which received only prophylactic immunization, but no sensitization (i.e. group P+/S−), neither prophylactic immunization nor sensitization (i.e. group PBS) or only sensitization (i.e. group P−/S+). In the therapeutic scheme, mice were sensitized s.c. with Bet v 1 (10 μg) adsorbed to aluminium hydroxide (three injections in 3 weeks intervals) followed by three s.c. immunizations with the peptide vaccine (i.e. group S+/T+). For control purposes, mice were not sensitized but received the peptide vaccine (i.e. group S−/T+) or were only sensitized (i.e. group S+/T−). In total, 7 groups of mice were studied (groups PBS, P+/S−, P+/S+, P−/S+, S+/T+, S+/T− and S−/T+). Blood samples were taken from the tail vein one day before each immunization and 3 weeks after the last immunization and were stored at −20°C until analysis. Mice were killed at day 120 to obtain spleen cells. Results were obtained in two independent sets of experiments. In the second experiment, two groups of mice were included which received a prophylactic or a therapeutic immunization with an irrelevant, Bet v 1-unrelated (i.e. grass pollen allergen Phl p 5-derived peptide) peptide coupled to KLH. In addition, groups of mice (n = 5) underwent the same prophylactic and therapeutic immunization protocol using either wild-type Bet v 1, or Bet v 1 fragments or a Bet v 1 trimer (10 μg/mouse) 24,25 as vaccines.

Bottom Line: The effects of peptide-specific and allergen-specific antibodies on T cell responses and allergic lung inflammation were studied using specific antibodies.Prophylactic and therapeutic vaccination of mice with the peptide vaccine induced Bet v 1-specific antibodies which suppressed Bet v 1-specific T cell responses and allergic lung inflammation.Vaccination with carrier-bound allergen-derived peptides lacking allergen-specific T cell epitopes induces allergen-specific IgG antibodies which suppress allergen-specific T cell responses and allergic lung inflammation.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

Show MeSH