Matrix-M™ adjuvanted envelope protein vaccine protects against lethal lineage 1 and 2 West Nile virus infection in mice

Sofia E. Magnusson, Karin H. Karlsson, Jenny M. Reimer, Silke Corbach-Söhle, Sameera Patel, Justin M. Richner, Norbert Nowotny, Luisa Barzon, Karin Lövgren Bengtsson, Sebastian Ulbert, Michael S. Diamond, Linda Stertman

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

West Nile virus (WNV) is a mosquito-transmitted flavivirus and an emerging pathogen in many parts of the world. In the elderly and immunosuppressed, infection can progress rapidly to debilitating and sometimes fatal neuroinvasive disease. Currently, no WNV vaccine is approved for use in humans. As there have been several recent outbreaks in the United States and Europe, there is an increasing need for a human WNV vaccine. In this study, we formulated the ectodomain of a recombinant WNV envelope (E) protein with the particulate saponin-based adjuvant Matrix-M™ and studied the antigen-specific immune responses in mice. Animals immunized with Matrix-M™ formulated E protein developed higher serum IgG1 and IgG2a and neutralizing antibody titers at antigen doses ranging from 0.5 to 10μg compared to those immunized with 3 or 10μg of E alone, E adjuvanted with 1% Alum, or with the inactivated virion veterinary vaccine, Duvaxyn® WNV. This phenotype was accompanied by strong cellular recall responses as splenocytes from mice immunized with Matrix-M™ formulated vaccine produced high levels of Th1 and Th2 cytokines. Addition of Matrix-M™ prolonged the duration of the immune response, as elevated humoral and cellular responses were maintained for more than 200 days. Importantly, mice vaccinated with Matrix-M™ formulated E protein were protected from lethal challenge with both lineage 1 and 2 WNV strains. In summary, Matrix-M™ adjuvanted E protein elicited potent and durable immune responses that prevented lethal WNV infection, and thus is a promising vaccine candidate for humans.

Original languageEnglish
Pages (from-to)800-808
Number of pages9
JournalVaccine
Volume32
Issue number7
DOIs
Publication statusPublished - Feb 7 2014

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West Nile Virus Vaccines
West Nile virus
Virus Diseases
Vaccines
vaccines
mice
infection
Proteins
proteins
Viral Envelope Proteins
Flavivirus
immune response
Histocompatibility Antigens Class II
Saponins
Neutralizing Antibodies
Culicidae
Virion
Disease Outbreaks
antigens
Immunoglobulin G

Keywords

  • Adjuvant
  • Matrix M™
  • Vaccine
  • West Nile virus

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Magnusson, S. E., Karlsson, K. H., Reimer, J. M., Corbach-Söhle, S., Patel, S., Richner, J. M., ... Stertman, L. (2014). Matrix-M™ adjuvanted envelope protein vaccine protects against lethal lineage 1 and 2 West Nile virus infection in mice. Vaccine, 32(7), 800-808. https://doi.org/10.1016/j.vaccine.2013.12.030

Matrix-M™ adjuvanted envelope protein vaccine protects against lethal lineage 1 and 2 West Nile virus infection in mice. / Magnusson, Sofia E.; Karlsson, Karin H.; Reimer, Jenny M.; Corbach-Söhle, Silke; Patel, Sameera; Richner, Justin M.; Nowotny, Norbert; Barzon, Luisa; Bengtsson, Karin Lövgren; Ulbert, Sebastian; Diamond, Michael S.; Stertman, Linda.

In: Vaccine, Vol. 32, No. 7, 07.02.2014, p. 800-808.

Research output: Contribution to journalArticle

Magnusson, SE, Karlsson, KH, Reimer, JM, Corbach-Söhle, S, Patel, S, Richner, JM, Nowotny, N, Barzon, L, Bengtsson, KL, Ulbert, S, Diamond, MS & Stertman, L 2014, 'Matrix-M™ adjuvanted envelope protein vaccine protects against lethal lineage 1 and 2 West Nile virus infection in mice', Vaccine, vol. 32, no. 7, pp. 800-808. https://doi.org/10.1016/j.vaccine.2013.12.030
Magnusson, Sofia E. ; Karlsson, Karin H. ; Reimer, Jenny M. ; Corbach-Söhle, Silke ; Patel, Sameera ; Richner, Justin M. ; Nowotny, Norbert ; Barzon, Luisa ; Bengtsson, Karin Lövgren ; Ulbert, Sebastian ; Diamond, Michael S. ; Stertman, Linda. / Matrix-M™ adjuvanted envelope protein vaccine protects against lethal lineage 1 and 2 West Nile virus infection in mice. In: Vaccine. 2014 ; Vol. 32, No. 7. pp. 800-808.
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