Fusion of C3d with hemagglutinin enhances protective immunity against swine influenza virus.
H1N1 and H3N2 are the dominant subtypes causing swine influenza in China and other countries. It is important to develop effective vaccines against both H1N1 and H3N2 subtypes of swine influenza virus (SIV). We examined the effects of a DNA vaccine expressing an influenza HA fused to three copies of murine complement C3d in mice. Plasmids encoding soluble HA (sHA), complete HA (tmHA), or a soluble fused form of HA (sHA-mC3d3) were constructed from the H3N2 subtype of SIV. The immune response was monitored by an enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition (HI) assays, and virus neutralization tests. Analysis of antibody titers indicated that immunization with HA-mC3d3 resulted in higher titers of anti-HA antibodies and higher antibody affinities, compared with serum from mice immunized with sHA or tmHA. Furthermore, the C3d fusion increased the Th2-biased immune response, by inducing IL-4 production. Splenocytes from mice immunized with sHA-mC3d3 produced about three-fold more IL-4 than did splenocytes from mice immunized with sHA or tmHA. Seven days post-challenge with homologous virus (H3N2), no virus was isolated from the mice immunized with HA-expressing plasmids. However, 10 days post-challenge with heterologous virus (H1N1), only mice immunized with sHA-mC3d3 had no virus or microscopic lesions in the kidneys and cerebrum. In conclusion, C3d enhanced antibody responses to hemagglutinin and protective immunity against SIV of different subtypes.
Li
Guo-Xin
GX
Division of Swine Infectious Diseases, National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 427 Maduan Street, Harbin 150001, Heilongjiang, China.
Tian
Zhi-Jun
ZJ
Yu
Hai
H
Jin
Yuan-Yuan
YY
Hou
Shao-Hua
SH
Zhou
Yan-Jun
YJ
Liu
Tian-Qiang
TQ
Hu
Shou-Ping
SP
Tong
Guang-Zhi
GZ
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D003001:Cloning, Molecular; D015933:Complement C3d / Q000235:genetics* / Q000276:immunology* / Q000627:therapeutic use; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006385:Hemagglutination Inhibition Tests; D006388:Hemagglutinins / Q000235:genetics / Q000627:therapeutic use*; D007109:Immunity; D007111:Immunity, Cellular; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000662:veterinary; D016133:Polymerase Chain Reaction; D017464:Receptors, Complement 3d / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D013552:Swine; D019444:Vaccines, DNA / Q000627:therapeutic use*
D017931:DNA Primers; D006388:Hemagglutinins; D017464:Receptors, Complement 3d; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D015933:Complement C3d