Potent adjuvant effects of novel NKT stimulatory glycolipids on hemagglutinin based DNA vaccine for H5N1 influenza virus.
H5N1 influenza virus is a highly pathogenic virus, posing a pandemic threat. Previously, we showed that phenyl analogs of α-galactosylceramide (α-GalCer) displayed greater NKT stimulation than α-GalCer. Here, we examined the adjuvant effects of one of the most potent analogs, C34, on consensus hemagglutinin based DNA vaccine (pCHA5) for H5N1 virus. Upon intramuscular electroporation of mice with pCHA5 with/without various α-GalCer analogs, C34-adjuvanted group developed the highest titer against consensus H5 and more HA-specific IFN-γ secreting CD8 cells (203±13.5) than pCHA5 alone (152.6±13.7, p<0.05). Upon lethal challenge of NIBRG-14 virus, C34-adjuvanted group (84.6%) displayed higher survival rate than pCHA5 only group (46.1%). In the presence of C34 as adjuvant, the antisera displayed broader and greater neutralizing activities against virions pseudotyped with HA of clade 1, and 2.2 than pCHA5 only group. Moreover, to simulate an emergency response to a sudden H5N1 outbreak, we injected mice intramuscularly with single dose of a new consensus H5 (pCHA5-II) based on 1192 full-length H5 sequences, with C34 as adjuvant. The latter not only enhanced the humoral immune response and protection against virus challenge, but also broadened the spectrum of neutralization against pseudotyped HA viruses. Our vaccine strategy can be easily implemented for any H5N1 virus outbreak by single IM injection of a consensus H5 DNA vaccine based on updated HA sequences using C34 as an adjuvant.
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan.
Jung-Tung
JT
Hung
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Yi-Chieh
YC
Tsai
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Graduate Institute of Life Science, National Defense Medical Center, Taipei 114, Taiwan.
Wen-Der
WD
Lin
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Jia-Tsrong
JT
Jan
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Kun-Hsien
KH
Lin
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Institute and Department of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan.
Jing-Rong
JR
Huang
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Graduate Institute of Life Science, National Defense Medical Center, Taipei 114, Taiwan.
Jing-Yan
JY
Cheng
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.
Ming-Wei
MW
Chen
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.
Chi-Huey
CH
Wong
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan. Electronic address: a1yu@ucsd.edu.
Alice L
AL
Yu
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D018274:Electroporation; D005260:Female; D006017:Glycolipids / Q000008:administration & dosage / Q000494:pharmacology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006017:Glycolipids; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA; C109963:hemagglutinin, avian influenza A virus; D007371:Interferon-gamma
Cross protection; Glycolipid; Influenza vaccine; iNKT