Protective efficacy of a broadly cross-reactive swine influenza DNA vaccine encoding M2e, cytotoxic T lymphocyte epitope and consensus H3 hemagglutinin.
BACKGROUND
Pigs have been implicated as mixing reservoir for the generation of new pandemic influenza strains, control of swine influenza has both veterinary and public health significance. Unlike human influenza vaccines, strains used for commercially available swine influenza vaccines are not regularly replaced, making the vaccines provide limited protection against antigenically diverse viruses. It is therefore necessary to develop broadly protective swine influenza vaccines that are efficacious to both homologous and heterologous virus infections. In this study, two forms of DNA vaccines were constructed, one was made by fusing M2e to consensus H3HA (MHa), which represents the majority of the HA sequences of H3N2 swine influenza viruses. Another was made by fusing M2e and a conserved CTL epitope (NP147-155) to consensus H3HA (MNHa). Their protective efficacies against homologous and heterologous challenges were tested.


RESULTS
BALB/c mice were immunized twice by particle-mediated epidermal delivery (gene gun) with the two DNA vaccines. It was shown that the two vaccines elicited substantial antibody responses, and MNHa induced more significant T cell-mediated immune response than MHa did. Then two H3N2 strains representative of different evolutional and antigenic clusters were used to challenge the vaccine-immunized mice (homosubtypic challenge). Results indicated that both of the DNA vaccines prevented homosubtypic virus infections completely. The vaccines' heterologous protective efficacies were further tested by challenging with a H1N1 swine influenza virus and a reassortant 2009 pandemic strain. It was found that MNHa reduced the lung viral titers significantly in both challenge groups, histopathological observation showed obvious reduction of lung pathogenesis as compared to MHa and control groups.


CONCLUSIONS
The combined utility of the consensus HA and the conserved M2e and CTL epitope can confer complete and partial protection against homologous and heterologous challenges, respectively, in mouse model. This may provide a basis for the development of universal swine influenza vaccines.
Division of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
Bin
B
Wang
Hai
H
Yu
Fu-Ru
FR
Yang
Meng
M
Huang
Ji-Hong
JH
Ma
Guang-Zhi
GZ
Tong
D000818:Animals; D004195:Disease Models, Animal; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000517:prevention & control*; D013552:Swine; D013553:Swine Diseases / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D000086082:Viroporin Proteins
D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins