Giuseppe
Emeritus
[Source: PLoS ONE, full text: (LINK). Abstract, edited.]
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Increased Immunogenicity and Protective Efficacy of Influenza M2e Fused to a Tetramerizing Protein
Anne-Marie Carola Andersson<SUP>1</SUP>, Kjell O. H?kansson<SUP>2</SUP>, Benjamin Anderschou Holbech Jensen<SUP>1</SUP>, Dennis Christensen<SUP>3</SUP>, Peter Andersen<SUP>3</SUP>, Allan Randrup Thomsen<SUP>1</SUP>, Jan Pravsgaard Christensen<SUP>1</SUP><SUP>*</SUP>
<SUP></SUP>
1 Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark, 2 Department of Biology, University of Copenhagen, Copenhagen, Denmark, 3 Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark
Abstract
The ectodomain of the matrix 2 protein (M2e) of influenza A virus represents an attractive target for developing a universal influenza A vaccine, with its sequence being highly conserved amongst human variants of this virus. With the aim of targeting conformational epitopes presumably shared by diverse influenza A viruses, a vaccine (M2e-NSP4) was constructed linking M2e (in its consensus sequence) to the rotavirus fragment NSP4<SUB>98?135</SUB>; due to its coiled-coil region this fragment is known to form tetramers in aqueous solution and in this manner we hoped to mimick the natural configuration of M2e as presented in membranes. M2e-NSP4 was then evaluated side-by-side with synthetic M2e peptide for its immunogenicity and protective efficacy in a murine influenza challenge model. Here we demonstrate that M2e fused to the tetramerizing protein induces an accelerated, augmented and more broadly reactive antibody response than does M2e peptide as measured in two different assays. Most importantly, vaccination with M2e-NSP4 caused a significant decrease in lung virus load early after challenge with influenza A virus and maintained its efficacy against a lethal challenge even at very low vaccine doses. Based on the results presented in this study M2e-NSP4 merits further investigation as a candidate for or as a component of a universal influenza A vaccine.
Citation: Andersson A-MC, H?kansson KO, Jensen BAH, Christensen D, Andersen P, et al. (2012) Increased Immunogenicity and Protective Efficacy of Influenza M2e Fused to a Tetramerizing Protein. PLoS ONE 7(10): e46395. doi:10.1371/journal.pone.0046395
Editor: Eliane Namie Miyaji, Instituto Butantan, Brazil
Received: June 22, 2012; Accepted: August 31, 2012; Published: October 1, 2012
Copyright: ? 2012 Andersson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the Lundbeck Foundation, The Danish Council for Strategic Research, The Danish Council for Independent Research, Health and Disease and Bertil Anderssons Foundation. The funding sources had no involvement in any decisions made regarding study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: JPC@sund.ku.dk
-Anne-Marie Carola Andersson<SUP>1</SUP>, Kjell O. H?kansson<SUP>2</SUP>, Benjamin Anderschou Holbech Jensen<SUP>1</SUP>, Dennis Christensen<SUP>3</SUP>, Peter Andersen<SUP>3</SUP>, Allan Randrup Thomsen<SUP>1</SUP>, Jan Pravsgaard Christensen<SUP>1</SUP><SUP>*</SUP>
<SUP></SUP>
1 Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark, 2 Department of Biology, University of Copenhagen, Copenhagen, Denmark, 3 Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark
Abstract
The ectodomain of the matrix 2 protein (M2e) of influenza A virus represents an attractive target for developing a universal influenza A vaccine, with its sequence being highly conserved amongst human variants of this virus. With the aim of targeting conformational epitopes presumably shared by diverse influenza A viruses, a vaccine (M2e-NSP4) was constructed linking M2e (in its consensus sequence) to the rotavirus fragment NSP4<SUB>98?135</SUB>; due to its coiled-coil region this fragment is known to form tetramers in aqueous solution and in this manner we hoped to mimick the natural configuration of M2e as presented in membranes. M2e-NSP4 was then evaluated side-by-side with synthetic M2e peptide for its immunogenicity and protective efficacy in a murine influenza challenge model. Here we demonstrate that M2e fused to the tetramerizing protein induces an accelerated, augmented and more broadly reactive antibody response than does M2e peptide as measured in two different assays. Most importantly, vaccination with M2e-NSP4 caused a significant decrease in lung virus load early after challenge with influenza A virus and maintained its efficacy against a lethal challenge even at very low vaccine doses. Based on the results presented in this study M2e-NSP4 merits further investigation as a candidate for or as a component of a universal influenza A vaccine.
Citation: Andersson A-MC, H?kansson KO, Jensen BAH, Christensen D, Andersen P, et al. (2012) Increased Immunogenicity and Protective Efficacy of Influenza M2e Fused to a Tetramerizing Protein. PLoS ONE 7(10): e46395. doi:10.1371/journal.pone.0046395
Editor: Eliane Namie Miyaji, Instituto Butantan, Brazil
Received: June 22, 2012; Accepted: August 31, 2012; Published: October 1, 2012
Copyright: ? 2012 Andersson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the Lundbeck Foundation, The Danish Council for Strategic Research, The Danish Council for Independent Research, Health and Disease and Bertil Anderssons Foundation. The funding sources had no involvement in any decisions made regarding study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: JPC@sund.ku.dk
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