copenhagen, 5 march 2015 identification of the most immunogenic/protective vlp-ha construct in mice...

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Copenhagen, 5 March 2015 Identification of the most immunogenic/protective VLP-HA construct in mice Department of Immunology Development of a universal influenza vaccine based on tandem core technology

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VLP-HA constructs ΔHA stalk (HA ): HA : HA : HA : LAH (HA ): HA : HA : HA : HA : HA :

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Page 1: Copenhagen, 5 March 2015 Identification of the most immunogenic/protective VLP-HA construct in mice Department of Immunology Development of a universal

Copenhagen, 5 March 2015

Identification of the most immunogenic/protective VLP-HA construct in mice

Department of Immunology

Development of a universal influenza vaccine based on tandem core technology

Page 2: Copenhagen, 5 March 2015 Identification of the most immunogenic/protective VLP-HA construct in mice Department of Immunology Development of a universal

Schematic of VLP-HA constructs

Modified from Steel et al, mBio 2010

ΔHA stalk (HA292-553):

GGGG

Page 3: Copenhagen, 5 March 2015 Identification of the most immunogenic/protective VLP-HA construct in mice Department of Immunology Development of a universal

VLP-HA constructsΔHA stalk (HA292-553):

HA292-351 :

HA306-474 :

HA403-474 :

LAH (HA420-474):

HA292-402 :

HA292-474 :

HA306-402 :

HA306-351 :

HA351-474 :

Page 4: Copenhagen, 5 March 2015 Identification of the most immunogenic/protective VLP-HA construct in mice Department of Immunology Development of a universal

Immune response to VLP-HAs

Page 5: Copenhagen, 5 March 2015 Identification of the most immunogenic/protective VLP-HA construct in mice Department of Immunology Development of a universal

Immunization with VLP-Has protects mice in vivo

ΔHA stalk (HA292-553):

HA306-474 :

HA403-474 :

LAH (HA420-474):

Page 6: Copenhagen, 5 March 2015 Identification of the most immunogenic/protective VLP-HA construct in mice Department of Immunology Development of a universal

IgG-specific antibody response of mice vaccinated with VLP-HAs

ΔHA stalk (HA292-553):

HA306-474 :

HA403-474 :

LAH (HA420-474):

Page 7: Copenhagen, 5 March 2015 Identification of the most immunogenic/protective VLP-HA construct in mice Department of Immunology Development of a universal

HA420-474 (LAH) of different HA subtypes

Page 8: Copenhagen, 5 March 2015 Identification of the most immunogenic/protective VLP-HA construct in mice Department of Immunology Development of a universal

Ongoing Work

• Immunization with new VLPs in mice

• In vivo challenge-protection assay with H3N2

• Micro-neutralization and ADCC assays