TY - JOUR
T1 - Matrix-M™ adjuvanted envelope protein vaccine protects against lethal lineage 1 and 2 West Nile virus infection in mice
AU - Magnusson, Sofia E.
AU - Karlsson, Karin H.
AU - Reimer, Jenny M.
AU - Corbach-Söhle, Silke
AU - Patel, Sameera
AU - Richner, Justin M.
AU - Nowotny, Norbert
AU - Barzon, Luisa
AU - Bengtsson, Karin Lövgren
AU - Ulbert, Sebastian
AU - Diamond, Michael S.
AU - Stertman, Linda
N1 - Funding Information:
This work was supported by the European Commission under FP7, project number 261426 (WINGS; Epidemiology, Diagnosis and Prevention of West Nile Virus in Europe).
PY - 2014/2/7
Y1 - 2014/2/7
N2 - 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.
AB - 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.
KW - Adjuvant
KW - Matrix M™
KW - Vaccine
KW - West Nile virus
UR - http://www.scopus.com/inward/record.url?scp=84892861608&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892861608&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2013.12.030
DO - 10.1016/j.vaccine.2013.12.030
M3 - Article
C2 - 24380682
AN - SCOPUS:84892861608
SN - 0264-410X
VL - 32
SP - 800
EP - 808
JO - Vaccine
JF - Vaccine
IS - 7
ER -