Title :

Porous Nanoparticles With Self-Adjuvanting M2e-Fusion Protein and Recombinant Hemagglutinin Provide Strong and Broadly Protective Immunity Against Influenza Virus Infections

Author(s) :

Bernasconi, Valentina [Auteur]
Bernocchi, Beatrice [Auteur]
Ye, Liang [Auteur]
Le, Minh-Quan [Auteur]
Omokanye, Ajibola [Auteur]
Carpentier, Rodolphe [Auteur]
Lille Inflammation Research International Center (LIRIC) - U995
Schon, Karin [Auteur]
Saelens, Xavier [Auteur]
Staeheli, Peter [Auteur]
Betbeder, Didier [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Lycke, Nils [Auteur]

Journal title :

Frontiers in immunology

Abbreviated title :

Front. Immunol.

Volume number :

9

Publication date :

2018-09-12

ISSN :

1664-3224

English keyword(s) :

Universal vaccine
mucosal vaccination
influenza A virus
CTA1-DD
maltodextrin nanoparticles
targeted adjuvant
nasal immunization

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Due to the high risk of an outbreak of pandemic influenza, the development of a broadly protective universal influenza vaccine is highly warranted. The design of such a vaccine has attracted attention and much focus has ...
Show more >Due to the high risk of an outbreak of pandemic influenza, the development of a broadly protective universal influenza vaccine is highly warranted. The design of such a vaccine has attracted attention and much focus has been given to nanoparticle-based influenza vaccines which can be administered intranasally. This is particularly interesting since, contrary to injectable vaccines, mucosal vaccines elicit local IgA and lung resident T cell immunity, which have been found to correlate with stronger protection in experimental models of influenza virus infections. Also, studies in human volunteers have indicated that pre-existing CD4 T cells correlate well to increased resistance against infection. We have previously developed a fusion protein with 3 copies of the ectodomain of matrix protein 2 (M2e), which is one of the most explored conserved influenza A virus antigens for a broadly protective vaccine known today. To improve the protective ability of the self-adjuvanting fusion protein, CTA1-3M2e-DD, we incorporated it into porous maltodextrin nanoparticles (NPLs). This proof-of-principle study demonstrates that the combined vaccine vector given intranasally enhanced immune protection against a live challenge infection and reduced the risk of virus transmission between immunized and unimmunized individuals. Most importantly, immune responses to NPLs that also contained recombinant hemagglutinin (HA) were strongly enhanced in a CTA1-enzyme dependent manner and we achieved broadly protective immunity against a lethal infection with heterosubtypic influenza virus. Immune protection was mediated by enhanced levels of lung resident CD4 T cells as well as anti-HA and -M2e serum IgG and local IgA antibodies.Show less >

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Research team(s) :

Therapeutic innovation targetting inflammation

Submission date :

2019-05-17T13:14:45Z