title: A Universal Influenza Vaccine Can Lead to Disease Exacerbation or Viral Control Depending on Delivery Strategies.
abstract: The development of influenza A virus (IAV) vaccines, which elicits cross-strain immunity against seasonal and pandemic viruses is a major public health goal. As pigs are susceptible to human, avian, and swine-adapted IAV, they would be key targets of so called universal IAV vaccines, for reducing both the zoonotic risk and the economic burden in the swine industry. They also are relevant preclinical models. However, vaccination with conserved IAV antigens (AGs) in pigs was reported to elicit disease exacerbation. In this study, we assessed whether delivery strategies, i.e., dendritic cell (DC) targeting by the intradermal (ID) or intramuscular (IM) routes, impact on the outcome of the vaccination with three conserved IAV AGs (M2e, NP, and HA2) in pigs. The AGs were addressed to CD11c by non-covalent binding to biotinylated anti-CD11c monoclonal antibody. The CD11c-targeted AGs given by the ID route exacerbated disease. Conversely, CD11c-targeted NP injected by the IM route promoted T cell response compared to non-targeted NP. Furthermore, the conserved IAV AGs injected by the IM route, independently of DC targeting, induced both a reduction of viral shedding and a broader IgG response as compared to the ID route. Our findings highlight in a relevant animal species that the route of vaccine delivery impacts on the protection induced by conserved IAV AGs and on vaccine adverse effects. Finally, our results indicate that HA2 stands as the most promising conserved IAV AG for universal vaccine development.
authors.affiliation: VIM-INRA-Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Bernelin-Cottet
authors.affiliation: VIM-INRA-Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Deloizy
authors.affiliation: Institute of Microbiology of the Czech Academy of Sciences, v.v.i , Prague , Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Stanek
authors.affiliation: INRA, UE1277, Plate-Forme d'Infectiologie Expérimentale, PFIE , Nouzilly , France.
authors.forename: Céline
authors.initials: C
authors.lastname: Barc
authors.affiliation: VIM-INRA-Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Edwige
authors.initials: E
authors.lastname: Bouguyon
authors.affiliation: VIM-INRA-Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Céline
authors.initials: C
authors.lastname: Urien
authors.affiliation: INRA, UE1277, Plate-Forme d'Infectiologie Expérimentale, PFIE , Nouzilly , France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Boulesteix
authors.affiliation: INRA, UE1277, Plate-Forme d'Infectiologie Expérimentale, PFIE , Nouzilly , France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Pezant
authors.affiliation: VIM-INRA-Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Charles-Adrien
authors.initials: CA
authors.lastname: Richard
authors.affiliation: VIM-INRA-Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Moudjou
authors.affiliation: VIM-INRA-Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Da Costa
authors.affiliation: VIM-INRA-Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Luc
authors.initials: L
authors.lastname: Jouneau
authors.affiliation: VIM-INRA-Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Chevalier
authors.affiliation: Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le Cancer, Paris, France; INSERM U1041, Unité de Régulation Immunitaire et Vaccinologie, Département Immunologie, Paris, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
authors.affiliation: Institute of Microbiology of the Czech Academy of Sciences, v.v.i , Prague , Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Sebo
authors.affiliation: VIM-INRA-Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bertho
authors.affiliation: VIM-INRA-Université Paris-Saclay , Jouy-en-Josas , France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schwartz-Cornil
keywords: dendritic cells; human; influenza; routes of administration; swine; vaccine