Heterosubtypic protection against influenza A induced by adenylate cyclase toxoids delivering conserved HA2 subunit of hemagglutinin

0396067 - MBÚ 2014 RIV NL eng J - Článek v odborném periodiku
Staneková, Z. - Adkins, Irena - Kosová, Martina - Janulíková, J. - Šebo, Peter - Varečková, E.
Heterosubtypic protection against influenza A induced by adenylate cyclase toxoids delivering conserved HA2 subunit of hemagglutinin.
Antiviral Research. Roč. 97, č. 1 (2013), s. 24-35. ISSN 0166-3542. E-ISSN 1872-9096
Grant CEP: GA ČR GA310/08/0447; GA ČR GP310/09/P582
Institucionální podpora: RVO:61388971
Klíčová slova: Bordetella adenylate cyclase toxoid * Influenza A infection * Cross-protection
Kód oboru RIV: FR - Farmakologie a lékárnická chemie
Impakt faktor: 3.434, rok: 2013

The protective efficacy of currently available influenza vaccines is restricted to vaccine strains and their close antigenic variants. A new strategy to obtain cross-protection against influenza is based on conserved antigens of influenza A viruses (IAV), which are able to elicit a protective immune response. Here we describe a vaccination approach involving the conserved stem part of hemagglutinin, the HA2 subunit, shared by different HA subtypes of IAV. To increase its immunogenicity, a novel strategy of antigen delivery to antigen presenting cells (APCs) has been used. The HA2 segment (residues 23-185) was inserted into a genetically detoxified adenylate cyclase toxoid (CyaA-E5) which specifically targets and penetrates CD11b-expressing dendritic cells. The CyaA-E5-HA2 toxoid induced HA2(93-102), HA2(96-104) and HA2(170-178)-specific and Th1 polarized T-cell responses, and also elicited strong broadly cross-reactive HA2-specific antibody response. BALB/c mice immunized with three doses of purified CyaA-E5-HA2 without any adjuvant recovered from influenza infection 2 days earlier than the control mock-immunized mice
Trvalý link: http://hdl.handle.net/11104/0223922