A non-human hepadnaviral adjuvant for hepatitis C virus-based genetic vaccines.
Human hepatitis B virus (HBV) core antigen (HBcAg) can act as an adjuvant in hepatitis C virus (HCV)-based DNA vaccines. Since two billion people are, or have been, in contact with HBV, one may question the use of human HBV sequences as adjuvant. We herein evaluated non-human stork hepatitis B virus core gene-sequences from stork as DNA vaccine adjuvants. Full-length and fragmented stork HBcAg gene-sequences were added to an HCV non-structural (NS) 3/4A gene (NS3/4A-stork-HBcAg). This resulted in an enhanced priming of HCV-specific IFN-γ and IL-2 responses in both wild-type (wt)- and NS3/4A-transgenic (Tg) mice, the latter with dysfunctional NS3/4A-specific T cells. The NS3/4A-stork-HBcAg vaccine primed NS3/4A-specific T cells in hepatitis B e antigen (HBeAg)-Tg mice with dysfunctional T cells to HBcAg and HBeAg. Repeated immunizations boosted expansion of IFN-γ and IL-2-producing NS3/4A-specific T cells in wt- and NS3/4A-Tg mice. Importantly, NS3/4A-stork-HBcAg-DNA induced in vivo long-term functional memory T cell responses, whose maintenance required CD4(+) T cells. Thus, avian HBcAg gene-sequences from stork can effectively act as a DNA vaccine adjuvant. This technology can most likely be universally expanded to other genetic vaccine antigens, as this completely avoids the use of sequences from a human virus where a pre-existing immunity may interfere with its adjuvant effect.
Department of Laboratory Medicine, Division of Clinical Microbiology, F68, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. Electronic address: Sepideh.Levander@ki.se.
Sepideh
S
Levander
Department of Laboratory Medicine, Division of Clinical Microbiology, F68, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. Electronic address: Matti.Sallberg@ki.se.
Matti
M
Sällberg
Department of Laboratory Medicine, Division of Clinical Microbiology, F68, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. Electronic address: Gustaf.Ahlen@ki.se.
Gustaf
G
Ahlén
Department of Laboratory Medicine, Division of Clinical Microbiology, F68, Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. Electronic address: Lars.Frelin@ki.se.
Lars
L
Frelin
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001717:Birds; D005260:Female; D056945:Hep G2 Cells; D016174:Hepacivirus; D015613:Hepadnaviridae / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006526:Hepatitis C / Q000517:prevention & control*; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000008:administration & dosage; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology*
D000276:Adjuvants, Immunologic; D006512:Hepatitis B Core Antigens; C000611649:IFNG protein, mouse; D007376:Interleukin-2; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; D018664:Interleukin-12; D007371:Interferon-gamma
Adjuvant; Delivery; Electroporation; Genetic vaccine; HCV; Hepatitis C virus