Feasibility of single-shot H5N1 influenza vaccine in ferrets, macaques and rabbits

• Published in: Vaccine Vol. 28; no. 51; pp. 8125 - 8131
• Main Authors: Heldens, J.G.M, Glansbeek, H.L, Hilgers, L.A.T, Haenen, B, Stittelaar, K.J, Osterhaus, A.D.M.E, van den Bosch, J.F
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 29.11.2010; Elsevier; Elsevier Limited
• Subjects: Adjuvant; Adjuvants; Adjuvants, Immunologic - administration & dosage; Allergy and Immunology; Aluminum; Animal species; Animals; Antibodies; Antibodies, Viral - blood; Applied microbiology; Autopsy; Avian flu; Biological and medical sciences; Blood; Body temperature; Cell culture; CoVaccine HT; Cross Reactions; Cross-reactivity; Female; Ferrets; Fever - chemically induced; Fundamental and applied biological sciences. Psychology; Hemagglutination Inhibition Tests; Hematology; Immunization; Immunization, Secondary - methods; Immunogenicity; Influenza; Influenza A Virus, H5N1 Subtype - immunology; Influenza H5N1; Influenza Vaccines - administration & dosage; Influenza Vaccines - adverse effects; Influenza Vaccines - immunology; Influenza virus; Injection; Injections, Intramuscular; Laboratory animals; Macaca; Male; Microbiology; Miscellaneous; Mustela; Pandemic; Pandemics; Production capacity; Rabbits; Side effects; Skin Diseases - chemically induced; Standard deviation; Studies; Vaccination; Vaccination - methods; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Inactivated - administration & dosage; Vaccines, Inactivated - adverse effects; Vaccines, Inactivated - immunology; Virology; Pandemic; Adjuvant; CoVaccine HT; Influenza H5N1; Fissipedia; Carnivora; Rabbit; Orthomyxoviridae; Vaccine; Lagomorpha; Virus; Vertebrata; Influenzavirus A; Mammalia; Influenza A virus; Immunological adjuvant; Ferret
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.09.097

Abstract The feasibility of a single-shot, low-dose vaccination against pandemic influenza was investigated. The immunogenicity and safety of whole inactivated, cell culture-derived H5N1 virus plus CoVaccine HT™ as adjuvant was tested in various animal species. In ferrets, doses of 4.0 and 7.5 μg H5N1 (NIBRG-14; A/Vietnam/1194/04; clade 1) without adjuvant gave low geometric mean haemagglutination inhibition (HI) titres (GMTs) of 21–65 three weeks after intramuscular (IM) injection. The addition of 0.25–4 mg CoVaccine HT™ resulted in GMTs of 255–1470 corresponding with 4–25-fold increases. A second immunization caused GMTs of 8914–23,525 two weeks later, which confirmed strong priming. One out of 8 ferrets injected with antigen alone and 5 out of 32 ferrets injected with adjuvanted H5N1 demonstrated minimal transient, local reactions and two animals immunized with adjuvanted H5N1 exhibited increased body temperature one day after injection. In macaques, 5 μg H5N1 with CoVaccine HT™ or aluminium hydroxide as adjuvant elicited GMTs of 172 and 11, respectively three weeks later. A second immunization resulted in GMTs of 1751 and 123, respectively four weeks later. Analysis of cross-reactivity of antibodies after the first immunization with NIBRG-14 adjuvanted plus CoVaccine HT™ revealed GMTs of 69 against NIBRG-23 (A/turkey/Turkey/1/05; clade 2.2) and 42 against IBCDC-RG-2 (A/Indonesia/5/05-like; clade 2.1.3) while titres with aluminium hydroxide were <10. After the second immunization with CoVaccine HT™, GMT against NIBRG-23 was 599 and against IBCDC-RG-2 254, while those with aluminium hydroxide were 23 and 13, respectively. No local or systemic adverse events were detected in macaques. Safety of 5 μg H5N1 plus 0, 2 or 4 mg CoVaccine HT™ was investigated in a repeated dose study in rabbits. Groups of 6 or 9 male and female animals were immunized IM three times at three week intervals. None of the animals exerted treatment-related adverse reactions during the study or at necropsy 3 or 4 days after treatment. We concluded that a low dose of whole inactivated influenza virus plus CoVaccine HT™ is a promising, single-shot vaccine against pandemic influenza.