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Vaccine
Available online 1 February 2013
In Press, Uncorrected Proof ? Note to users
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Cross-protective immunity against multiple influenza virus subtypes by a novel modified vaccinia Ankara (MVA) vectored vaccine in mice
Joseph N. Brewooa, b, Corresponding author contact information, E-mail the corresponding author,
Tim D. Powella, b,
Jeremy C. Jonesa, b, 1,
Nancy A. Gundlacha, b, 2,
Ginger R. Younga, b,
Subash C. Dasa, b,
Charalambos D. Partidosa, b,
Dan T. Stinchcomba, b,
Jorge E. Osorioa, b, c
a Inviragen, Inc., 6502 Odana Rd, Madison, WI 53719, USA
b Inviragen, Inc., 1613 Prospect Pkwy, Ste 100, Ft. Collins, CO 80525, USA
c Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA
http://dx.doi.org/10.1016/j.vaccine.2013.01.038, How to Cite or Link Using DOI
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Abstract
Development of an influenza vaccine that provides cross-protective immunity remains a challenge. Candidate vaccines based on a recombinant modified vaccinia Ankara (MVA) viral vector expressing antigens from influenza (MVA/Flu) viruses were constructed. A vaccine candidate, designated MVA/HA1/C13L/NP, that expresses the hemagglutinin from pandemic H1N1 (A/California/04/09) and the nucleoprotein (N1) from highly pathogenic H5N1 (A/Vietnam/1203/04) fused to a secretory signal sequence from vaccinia virus was highly protective. The vaccine elicited strong antibody titers to homologous H1N1 viruses while cross-reactive antibodies to heterologous viruses were not detectable. In mice, this MVA/HA1/C13L/NP vaccine conferred complete protection against lethal challenge with A/Vietnam/1203/04 (H5N1), A/Norway/3487-2/09 (pandemic H1N1) or A/Influenza/Puerto Rico/8/34 (seasonal H1N1) and partial protection (57.1%) against challenge with seasonal H3N2 virus (A/Aichi/68). The protective efficacy of the vaccine was not affected by pre-existing immunity to vaccinia. Our findings highlight MVA as suitable vector to express multiple influenza antigens that could afford broad cross-protective immunity against multiple subtypes of influenza virus.
Highlights
► We have developed an influenza vaccine with cross protective immunity. ► The vaccine fully protects against seasonal and pandemic H1N1 influenza viruses in mice. ► Vaccine also fully protects against H5N1 influenza virus. ► Vaccine has the potential to protect against small pox virus.
http://www.sciencedirect.com/science/article/pii/S0264410X13001060
Available online 1 February 2013
In Press, Uncorrected Proof ? Note to users
Cover image
Cross-protective immunity against multiple influenza virus subtypes by a novel modified vaccinia Ankara (MVA) vectored vaccine in mice
Joseph N. Brewooa, b, Corresponding author contact information, E-mail the corresponding author,
Tim D. Powella, b,
Jeremy C. Jonesa, b, 1,
Nancy A. Gundlacha, b, 2,
Ginger R. Younga, b,
Subash C. Dasa, b,
Charalambos D. Partidosa, b,
Dan T. Stinchcomba, b,
Jorge E. Osorioa, b, c
a Inviragen, Inc., 6502 Odana Rd, Madison, WI 53719, USA
b Inviragen, Inc., 1613 Prospect Pkwy, Ste 100, Ft. Collins, CO 80525, USA
c Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA
http://dx.doi.org/10.1016/j.vaccine.2013.01.038, How to Cite or Link Using DOI
Permissions & Reprints
View full text
Purchase $31.50
Abstract
Development of an influenza vaccine that provides cross-protective immunity remains a challenge. Candidate vaccines based on a recombinant modified vaccinia Ankara (MVA) viral vector expressing antigens from influenza (MVA/Flu) viruses were constructed. A vaccine candidate, designated MVA/HA1/C13L/NP, that expresses the hemagglutinin from pandemic H1N1 (A/California/04/09) and the nucleoprotein (N1) from highly pathogenic H5N1 (A/Vietnam/1203/04) fused to a secretory signal sequence from vaccinia virus was highly protective. The vaccine elicited strong antibody titers to homologous H1N1 viruses while cross-reactive antibodies to heterologous viruses were not detectable. In mice, this MVA/HA1/C13L/NP vaccine conferred complete protection against lethal challenge with A/Vietnam/1203/04 (H5N1), A/Norway/3487-2/09 (pandemic H1N1) or A/Influenza/Puerto Rico/8/34 (seasonal H1N1) and partial protection (57.1%) against challenge with seasonal H3N2 virus (A/Aichi/68). The protective efficacy of the vaccine was not affected by pre-existing immunity to vaccinia. Our findings highlight MVA as suitable vector to express multiple influenza antigens that could afford broad cross-protective immunity against multiple subtypes of influenza virus.
Highlights
► We have developed an influenza vaccine with cross protective immunity. ► The vaccine fully protects against seasonal and pandemic H1N1 influenza viruses in mice. ► Vaccine also fully protects against H5N1 influenza virus. ► Vaccine has the potential to protect against small pox virus.
http://www.sciencedirect.com/science/article/pii/S0264410X13001060