A single immunization with CoVaccine HT-adjuvanted H5N1 influenza virus vaccine induces protective cellular and humoral immune responses in ferrets.
Highly pathogenic avian influenza A viruses of the H5N1 subtype continue to circulate in poultry, and zoonotic transmissions are reported frequently. Since a pandemic caused by these highly pathogenic viruses is still feared, there is interest in the development of influenza A/H5N1 virus vaccines that can protect humans against infection, preferably after a single vaccination with a low dose of antigen. Here we describe the induction of humoral and cellular immune responses in ferrets after vaccination with a cell culture-derived whole inactivated influenza A virus vaccine in combination with the novel adjuvant CoVaccine HT. The addition of CoVaccine HT to the influenza A virus vaccine increased antibody responses to homologous and heterologous influenza A/H5N1 viruses and increased virus-specific cell-mediated immune responses. Ferrets vaccinated once with a whole-virus equivalent of 3.8 microg hemagglutinin (HA) and CoVaccine HT were protected against homologous challenge infection with influenza virus A/VN/1194/04. Furthermore, ferrets vaccinated once with the same vaccine/adjuvant combination were partially protected against infection with a heterologous virus derived from clade 2.1 of H5N1 influenza viruses. Thus, the use of the novel adjuvant CoVaccine HT with cell culture-derived inactivated influenza A/H5N1 virus antigen is a promising and dose-sparing vaccine approach warranting further clinical evaluation.
Bodewes
R
R
Department of Virology, Erasmus Medical Center, Dr Molewaterplein 50, PO Box 2040, 3000 CA Rotterdam, Netherlands.
Kreijtz
J H C M
JH
van Amerongen
G
G
Geelhoed-Mieras
M M
MM
Verburgh
R J
RJ
Heldens
J G M
JG
Bedwell
J
J
van den Brand
J M A
JM
Kuiken
T
T
van Baalen
C A
CA
Fouchier
R A M
RA
Osterhaus
A D M E
AD
Rimmelzwaan
G F
GF
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001835:Body Weight; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D005434:Flow Cytometry; D006385:Hemagglutination Inhibition Tests; D006651:Histocytochemistry; D007150:Immunohistochemistry; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000473:pathology / Q000821:virology; D008853:Microscopy; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D010614:Pharynx / Q000821:virology; D014611:Vaccination / Q000379:methods*; D015164:Vaccines, Inactivated / Q000276:immunology
D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated