tetano
Editor, Senior Moderator
Vaccine
Available online 13 March 2013
In Press, Uncorrected Proof ? Note to users
Cover image
A polyvalent influenza A DNA vaccine induces heterologous immunity and protects pigs against pandemic A(H1N1)pdm09 virus infection
Karoline Bragstada,
Lasse Vinnera, 1,
Mette Sif Hansenb,
Jens Nielsenb,
Anders Fomsgaarda, c, Corresponding author contact information, E-mail the corresponding author
a Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen DK-2300, Denmark
b Division of Virology, DTU National Veterinary Institute, Lindholm, Kalvehave, DK-4771, Denmark
c Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark, Sdr. Boulevard, Odense DK-5000, Denmark
http://dx.doi.org/10.1016/j.vaccine.2013.02.061
Abstract
The composition of current influenza protein vaccines has to be reconsidered every season to match the circulating influenza viruses, continuously changing antigenicity. Thus, influenza vaccines inducing a broad cross-reactive immune response would be a great advantage for protection against both seasonal and emerging influenza viruses. We have developed an alternative influenza vaccine based on DNA expressing selected influenza proteins of pandemic and seasonal origin. In the current study, we investigated the protection of a polyvalent influenza DNA vaccine approach in pigs. We immunised pigs intradermally with a combination of influenza DNA vaccine components based on the pandemic 1918 H1N1 (M and NP genes), pandemic 2009 H1N1pdm09 (HA and NA genes) and seasonal 2005 H3N2 genes (HA and NA genes) and investigated the protection against infection with virus both homologous and heterologous to the DNA vaccine components.
We found that pigs challenged with a virus homologous to the HA and NA DNA vaccine components were well protected from infection. In addition, heterologous challenge virus was cleared rapidly compared to the unvaccinated control pigs. Immunisation by electroporation induced HI antibodies >40 HAU/ml seven days after second vaccination. Heterologous virus challenge as long as ten weeks after last immunisation was able to trigger a vaccine antibody HI response 26 times higher than in the control pigs. The H3N2 DNA vaccine HA and NA genes also triggered an effective vaccine response with protective antibody titres towards heterologous H3N2 virus.
The described influenza DNA vaccine is able to induce broadly protective immune responses even in a larger animal, like the pig, against both heterologous and homologous virus challenges despite relatively low HI titres after vaccination. The ability of this DNA vaccine to limit virus shedding may have an impact on virus spread among pigs which could possibly extend to humans as well, thereby diminishing the risk for epidemics and pandemics to evolve.
Highlights
?
Influenza A(H1N1)pdm09 DNA vaccine protects pigs against heterologous challenge.
?
DNA vaccine based on pandemic 1918 and 2009 genes induces cross-protective immunity.
?
DNA vaccine is highly efficient in influenza virus clearance.
?
DNA vaccine induces immunity and protection in a higher animal model, the pig.
?
Protection against influenza is not merely dependent on HI antibodies
http://www.sciencedirect.com/science/article/pii/S0264410X13002508
Available online 13 March 2013
In Press, Uncorrected Proof ? Note to users
Cover image
A polyvalent influenza A DNA vaccine induces heterologous immunity and protects pigs against pandemic A(H1N1)pdm09 virus infection
Karoline Bragstada,
Lasse Vinnera, 1,
Mette Sif Hansenb,
Jens Nielsenb,
Anders Fomsgaarda, c, Corresponding author contact information, E-mail the corresponding author
a Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen DK-2300, Denmark
b Division of Virology, DTU National Veterinary Institute, Lindholm, Kalvehave, DK-4771, Denmark
c Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark, Sdr. Boulevard, Odense DK-5000, Denmark
http://dx.doi.org/10.1016/j.vaccine.2013.02.061
Abstract
The composition of current influenza protein vaccines has to be reconsidered every season to match the circulating influenza viruses, continuously changing antigenicity. Thus, influenza vaccines inducing a broad cross-reactive immune response would be a great advantage for protection against both seasonal and emerging influenza viruses. We have developed an alternative influenza vaccine based on DNA expressing selected influenza proteins of pandemic and seasonal origin. In the current study, we investigated the protection of a polyvalent influenza DNA vaccine approach in pigs. We immunised pigs intradermally with a combination of influenza DNA vaccine components based on the pandemic 1918 H1N1 (M and NP genes), pandemic 2009 H1N1pdm09 (HA and NA genes) and seasonal 2005 H3N2 genes (HA and NA genes) and investigated the protection against infection with virus both homologous and heterologous to the DNA vaccine components.
We found that pigs challenged with a virus homologous to the HA and NA DNA vaccine components were well protected from infection. In addition, heterologous challenge virus was cleared rapidly compared to the unvaccinated control pigs. Immunisation by electroporation induced HI antibodies >40 HAU/ml seven days after second vaccination. Heterologous virus challenge as long as ten weeks after last immunisation was able to trigger a vaccine antibody HI response 26 times higher than in the control pigs. The H3N2 DNA vaccine HA and NA genes also triggered an effective vaccine response with protective antibody titres towards heterologous H3N2 virus.
The described influenza DNA vaccine is able to induce broadly protective immune responses even in a larger animal, like the pig, against both heterologous and homologous virus challenges despite relatively low HI titres after vaccination. The ability of this DNA vaccine to limit virus shedding may have an impact on virus spread among pigs which could possibly extend to humans as well, thereby diminishing the risk for epidemics and pandemics to evolve.
Highlights
?
Influenza A(H1N1)pdm09 DNA vaccine protects pigs against heterologous challenge.
?
DNA vaccine based on pandemic 1918 and 2009 genes induces cross-protective immunity.
?
DNA vaccine is highly efficient in influenza virus clearance.
?
DNA vaccine induces immunity and protection in a higher animal model, the pig.
?
Protection against influenza is not merely dependent on HI antibodies
http://www.sciencedirect.com/science/article/pii/S0264410X13002508