tetano
Editor, Senior Moderator
Antiviral Res. 2012 Oct 1. pii: S0166-3542(12)00205-7. doi: 10.1016/j.antiviral.2012.09.008. [Epub ahead of print]
Heterosubtypic protection against influenza induced by adenylate cyclase toxoids delivering conserved HA2 subunit of hemagglutinin.
Stanekov? Z, Adkins I, Kosov? M, Janul?kov? J, Sebo P, Varečkov? E.
Source
Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Abstract
The protective efficacy of currently available influenza vaccines is restricted to vaccine strains and their close antigenic variants. A new strategy to obtain a 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. More importantly, immunized mice were protected against a lethal challenge with 2LD(50) dose of a homologous virus (H3 subtype), as well as against the infection with a heterologous (H7 subtype) influenza A virus. This is the first report on heterosubtypic protection against influenza A infection mediated by HA2-based vaccine that can induce both humoral and cellular immune responses without the need of adjuvant.
Copyright ? 2012. Published by Elsevier B.V.
PMID:
23036818
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23036818
Heterosubtypic protection against influenza induced by adenylate cyclase toxoids delivering conserved HA2 subunit of hemagglutinin.
Stanekov? Z, Adkins I, Kosov? M, Janul?kov? J, Sebo P, Varečkov? E.
Source
Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Abstract
The protective efficacy of currently available influenza vaccines is restricted to vaccine strains and their close antigenic variants. A new strategy to obtain a 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. More importantly, immunized mice were protected against a lethal challenge with 2LD(50) dose of a homologous virus (H3 subtype), as well as against the infection with a heterologous (H7 subtype) influenza A virus. This is the first report on heterosubtypic protection against influenza A infection mediated by HA2-based vaccine that can induce both humoral and cellular immune responses without the need of adjuvant.
Copyright ? 2012. Published by Elsevier B.V.
PMID:
23036818
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23036818