Hemozoin is a potent adjuvant for hemagglutinin split vaccine without pyrogenicity in ferrets.
BACKGROUND
Synthetic hemozoin (sHZ, also known as β-hematin) from monomeric heme is a particle adjuvant which activates antigen-presenting cells (APCs), such as dendritic cells and macrophages, and enhances humoral immune responses to several antigens, including ovalbumin, human serum albumin, and serine repeat antigen 36 of Plasmodium falciparum. In the present study, we evaluated the adjuvanticity and pyrogenicity of sHZ as an adjuvant for seasonal trivalent hemagglutinin split vaccine (SV) for humans using the experimental ferret model.


METHODS
Ferrets were twice immunized with trivalent SV, SV with sHZ (SV/sHZ) or Fluad, composed of trivalent SV with MF59. Serum hemagglutination inhibition (HI) titers against three viral hemagglutinin (HA) antigens were measured at every week after the immunization. The pyrogenicity of SV/sHZ was examined by monitoring the body temperature of the immunized ferrets. To evaluate the protective efficacy of SV/sHZ, the immunized ferrets were challenged with influenza virus B infection, followed by measurement of viral titers in the nasal cavity and body temperature.


RESULTS
sHZ enhanced HI titers against three viral HA antigens in a dose-dependent manner, to an extent comparable to that of Fluad. The highest dose of sHZ (800 μg) immunized with SV conferred sterile protection against infection with heterologous Influenza B virus, without causing any pyrogenic reaction such as high fever.


CONCLUSIONS
In the present study, sHZ enhanced the protective efficacy of SV against influenza infection without inducing pyrogenic reaction, suggesting sHZ to be a promising adjuvant candidate for human SV.
Infectious Diseases, Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan; Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation (NIBIO), Osaka, Japan; Laboratory of Vaccine Science, Immunology Frontier Research Center (IFREC), World Premier Institute (WPI), Osaka University, Osaka, Japan.
Motoyasu
M
Onishi
Infectious Diseases, Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Mitsutaka
M
Kitano
Infectious Diseases, Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Keiichi
K
Taniguchi
Infectious Diseases, Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Tomoyuki
T
Homma
Infectious Diseases, Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Masanori
M
Kobayashi
Infectious Diseases, Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Akihiko
A
Sato
Laboratory of Malaria Immunology, Immunology Frontier Research Center (IFREC), World Premier Institute (WPI), Osaka University, Osaka, Japan.
Cevayir
C
Coban
Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation (NIBIO), Osaka, Japan; Laboratory of Vaccine Science, Immunology Frontier Research Center (IFREC), World Premier Institute (WPI), Osaka University, Osaka, Japan. Electronic address: kenishii@biken.osaka-u.ac.jp.
Ken J
KJ
Ishii
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001831:Body Temperature; D005260:Female; D005289:Ferrets; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006420:Hemeproteins / Q000008:administration & dosage*; D009981:Influenza B virus; D007252:Influenza Vaccines / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006420:Hemeproteins; D007252:Influenza Vaccines; C020753:hemozoin
Adjuvant; Ferret; Fluad; Influenza; Seasonal trivalent HA split vaccine; Vaccine