Skip to main content
Top
Published in: Immunologic Research 2/2018

Open Access 01-04-2018 | Original Article

Matrix-M™ adjuvant enhances immunogenicity of both protein- and modified vaccinia virus Ankara-based influenza vaccines in mice

Authors: Sofia E. Magnusson, Arwen F. Altenburg, Karin Lövgren Bengtsson, Fons Bosman, Rory D. de Vries, Guus F. Rimmelzwaan, Linda Stertman

Published in: Immunologic Research | Issue 2/2018

Login to get access

Abstract

Influenza viruses continuously circulate in the human population and escape recognition by virus neutralizing antibodies induced by prior infection or vaccination through accumulation of mutations in the surface proteins hemagglutinin (HA) and neuraminidase (NA). Various strategies to develop a vaccine that provides broad protection against different influenza A viruses are under investigation, including use of recombinant (r) viral vectors and adjuvants. The replication-deficient modified vaccinia virus Ankara (MVA) is a promising vaccine vector that efficiently induces B and T cell responses specific for the antigen of interest. It is assumed that live vaccine vectors do not require an adjuvant to be immunogenic as the vector already mediates recruitment and activation of immune cells. To address this topic, BALB/c mice were vaccinated with either protein- or rMVA-based HA influenza vaccines, formulated with or without the saponin-based Matrix-M™ adjuvant. Co-formulation with Matrix-M significantly increased HA vaccine immunogenicity, resulting in antigen-specific humoral and cellular immune responses comparable to those induced by unadjuvanted rMVA-HA. Of special interest, rMVA-HA immunogenicity was also enhanced by addition of Matrix-M, demonstrated by enhanced HA inhibition antibody titres and cellular immune responses. Matrix-M added to either protein- or rMVA-based HA vaccines mediated recruitment and activation of antigen-presenting cells and lymphocytes to the draining lymph node 24 and 48 h post-vaccination. Taken together, these results suggest that adjuvants can be used not only with protein-based vaccines but also in combination with rMVA to increase vaccine immunogenicity, which may be a step forward to generate new and more effective influenza vaccines.
Appendix
Available only for authorised users
Literature
3.
go back to reference Wright PF, Neumann G, Kawaoka Y. Orthomyxoviruses. In: Knipe DM, Howley PM, Cohen JI, Griffin DE, Lamb RA, Martin MA, et al., editors. Fields virology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2013. p. 1186–243. Wright PF, Neumann G, Kawaoka Y. Orthomyxoviruses. In: Knipe DM, Howley PM, Cohen JI, Griffin DE, Lamb RA, Martin MA, et al., editors. Fields virology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2013. p. 1186–243.
8.
go back to reference Shaw ML, Palese P. Orthomyxoviridae. In: Knipe DM, Howley PM, Cohen JI, Griffin DE, Lamb RA, Martin MA, et al., editors. Fields virology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2013. p. 1151–85. Shaw ML, Palese P. Orthomyxoviridae. In: Knipe DM, Howley PM, Cohen JI, Griffin DE, Lamb RA, Martin MA, et al., editors. Fields virology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2013. p. 1151–85.
9.
go back to reference Skowronski DM, Chambers C, Sabaiduc S, De Serres G, Dickinson JA, Winter AL et al. Interim estimates of 2014/15 vaccine effectiveness against influenza A(H3N2) from Canada’s Sentinel Physician Surveillance Network, January 2015. Euro surveill. 2015;20(4). Skowronski DM, Chambers C, Sabaiduc S, De Serres G, Dickinson JA, Winter AL et al. Interim estimates of 2014/15 vaccine effectiveness against influenza A(H3N2) from Canada’s Sentinel Physician Surveillance Network, January 2015. Euro surveill. 2015;20(4).
10.
go back to reference Pebody RG, Warburton F, Ellis J, Andrews N, Thompson C, von Wissmann B, et al. Low effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2014/15 mid-season results. Euro surveill. 2015;20(5):21025.CrossRefPubMed Pebody RG, Warburton F, Ellis J, Andrews N, Thompson C, von Wissmann B, et al. Low effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2014/15 mid-season results. Euro surveill. 2015;20(5):21025.CrossRefPubMed
11.
go back to reference Flannery B, Clippard J, Zimmerman RK, Nowalk MP, Jackson ML, Jackson LA, et al. Early estimates of seasonal influenza vaccine effectiveness—United States, January 2015. MMWR Morb Mortal Wkly Rep. 2015;64(1):10–5.PubMedPubMedCentral Flannery B, Clippard J, Zimmerman RK, Nowalk MP, Jackson ML, Jackson LA, et al. Early estimates of seasonal influenza vaccine effectiveness—United States, January 2015. MMWR Morb Mortal Wkly Rep. 2015;64(1):10–5.PubMedPubMedCentral
15.
go back to reference Overton ET, Stapleton J, Frank I, Hassler S, Goepfert PA, Barker D, et al. Safety and immunogenicity of modified vaccinia Ankara-Bavarian Nordic smallpox vaccine in vaccinia-naive and experienced human immunodeficiency virus-infected individuals: an open-label, controlled clinical phase II trial. Open Forum Infect Dis. 2015;2(2):ofv040. https://doi.org/10.1093/ofid/ofv040.CrossRefPubMedPubMedCentral Overton ET, Stapleton J, Frank I, Hassler S, Goepfert PA, Barker D, et al. Safety and immunogenicity of modified vaccinia Ankara-Bavarian Nordic smallpox vaccine in vaccinia-naive and experienced human immunodeficiency virus-infected individuals: an open-label, controlled clinical phase II trial. Open Forum Infect Dis. 2015;2(2):ofv040. https://​doi.​org/​10.​1093/​ofid/​ofv040.CrossRefPubMedPubMedCentral
17.
go back to reference Frey S, Poland G, Percell S, Podda A. Comparison of the safety, tolerability, and immunogenicity of a MF59-adjuvanted influenza vaccine and a non-adjuvanted influenza vaccine in non-elderly adults. Vaccine. 2003;21(27–30):4234–7.CrossRefPubMed Frey S, Poland G, Percell S, Podda A. Comparison of the safety, tolerability, and immunogenicity of a MF59-adjuvanted influenza vaccine and a non-adjuvanted influenza vaccine in non-elderly adults. Vaccine. 2003;21(27–30):4234–7.CrossRefPubMed
22.
go back to reference Study of parenterally administrated adjuvanted seasonal influenza vaccine in healthy elderly volunteers. Identifier: NCT01444482. Study of parenterally administrated adjuvanted seasonal influenza vaccine in healthy elderly volunteers. Identifier: NCT01444482.
25.
go back to reference Osterhaus AD, Rimmelzwaan GF. Induction of virus-specific immunity by iscoms. Dev Biol Stand. 1998;92:49–58.PubMed Osterhaus AD, Rimmelzwaan GF. Induction of virus-specific immunity by iscoms. Dev Biol Stand. 1998;92:49–58.PubMed
36.
go back to reference Lovgren K, Morein B. The requirement of lipids for the formation of immunostimulating complexes (iscoms). Biotechnol Appl Biochem. 1988;10(2):161–72.PubMed Lovgren K, Morein B. The requirement of lipids for the formation of immunostimulating complexes (iscoms). Biotechnol Appl Biochem. 1988;10(2):161–72.PubMed
37.
go back to reference Kreijtz JH, Suezer Y, van Amerongen G, de Mutsert G, Schnierle BS, Wood JM, et al. Recombinant modified vaccinia virus Ankara-based vaccine induces protective immunity in mice against infection with influenza virus H5N1. J Infect Dis. 2007;195(11):1598–606. https://doi.org/10.1086/517614.CrossRefPubMed Kreijtz JH, Suezer Y, van Amerongen G, de Mutsert G, Schnierle BS, Wood JM, et al. Recombinant modified vaccinia virus Ankara-based vaccine induces protective immunity in mice against infection with influenza virus H5N1. J Infect Dis. 2007;195(11):1598–606. https://​doi.​org/​10.​1086/​517614.CrossRefPubMed
38.
go back to reference Palmer D.F. DWR, Coleman M.T. and Schild G.C. Advanced laboratory technicals for immunological diagnostics. In: Welfare USDHE, editor. Atlanta1975. p. 25–62. Palmer D.F. DWR, Coleman M.T. and Schild G.C. Advanced laboratory technicals for immunological diagnostics. In: Welfare USDHE, editor. Atlanta1975. p. 25–62.
40.
go back to reference Caux C, Vanbervliet B, Massacrier C, Azuma M, Okumura K, Lanier LL, et al. B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J Exp Med. 1994;180(5):1841–7.CrossRefPubMed Caux C, Vanbervliet B, Massacrier C, Azuma M, Okumura K, Lanier LL, et al. B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J Exp Med. 1994;180(5):1841–7.CrossRefPubMed
Metadata
Title
Matrix-M™ adjuvant enhances immunogenicity of both protein- and modified vaccinia virus Ankara-based influenza vaccines in mice
Authors
Sofia E. Magnusson
Arwen F. Altenburg
Karin Lövgren Bengtsson
Fons Bosman
Rory D. de Vries
Guus F. Rimmelzwaan
Linda Stertman
Publication date
01-04-2018
Publisher
Springer US
Published in
Immunologic Research / Issue 2/2018
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-018-8991-x

Other articles of this Issue 2/2018

Immunologic Research 2/2018 Go to the issue