Evaluation of safety and immunogenicity of recombinant influenza hemagglutinin (H5/Indonesia/05/2005) formulated with and without a stable oil-in-water emulsion containing glucopyranosyl-lipid A (SE+GLA) adjuvant

• Published in: Vaccine Vol. 31; no. 48; pp. 5760 - 5765
• Main Authors: Treanor, John J., Essink, Brandon, Hull, Steven, Reed, Steven, Izikson, Ruvim, Patriarca, Peter, Goldenthal, Karen L., Kohberger, Robert, Dunkle, Lisa M.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 19.11.2013; Elsevier; Elsevier Limited
• Subjects: Adjuvants; Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - adverse effects; Adolescent; Adult; adults; Allergy and Immunology; Animals; Antibodies, Viral - blood; Antigens; Applied microbiology; Avian flu; Baculovirus; Biological and medical sciences; blood serum; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - pathology; Emergency medical care; Emulsions; Emulsions - administration & dosage; Emulsions - adverse effects; Female; Fundamental and applied biological sciences. Psychology; H5N1; Healthy Volunteers; hemagglutination; Hemagglutination Inhibition Tests; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; hemagglutinins; Hospitalization; Humans; Hydration; Immunization; Immunogenicity; influenza; Influenza Vaccines - administration & dosage; Influenza Vaccines - adverse effects; Influenza Vaccines - immunology; injection site; Insects; Licenses; lipid A; Lipid A - administration & dosage; Lipid A - adverse effects; Lipid A - analogs & derivatives; Lipids; Male; Microbiology; Middle Aged; Miscellaneous; Mortality; Mutation; Pain; pandemic; Pandemic influenza; Pandemics; Placebos - administration & dosage; Proteins; recombinant DNA; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Studies; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - adverse effects; Vaccines, Synthetic - immunology; Virology; Viruses; Young Adult; Asia; South east Asia; Indonesia; H5N1; Adjuvants; Vaccines; Pandemic influenza; Hemagglutinin; Tropical zone; Orthomyxoviridae; Zoopathogen; Vaccine; Infection; Virus; Influenzavirus A; Immunogenicity; Avian influenzavirus; Viral disease; Immunological adjuvant; Influenza
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2013.08.064

•We evaluated baculovirus-expressed recombinant H5 hemagglutinin vaccine with the adjuvant GLE/SE.•Adjuvanted vaccine was substantially more immunogenic at all dose levels than the unadjuvanted vaccine.•Even at the lowest dose of vaccine administered, serum HAI antibody responses of ≥1:40 were seen in 72% of subjects.•GLA/SE is an effective adjuvant for recombinant H5 HA.•Baculovirus-expressed HA vaccine has promise for pandemic preparedness as well. Expression of recombinant hemagglutinin (rHA) in insect cells represents a technology with proven efficacy in seasonal influenza and with the potential for a rapid response to the emergence of new, pandemic strains. We evaluated the safety and immunogenicity of rHA vaccine (H5/Indonesia/5/05) produced in SF+ insect cells using a baculovirus expression vector system (BEVS). The rHA vaccine was tested with and without the adjuvant glucopyranosyl lipid A/stable emulsion (GLA/SE). Healthy adults 18–49 were randomized to two IM doses on Days 0 and 21 of placebo; unadjuvanted rHA 135μg or 45μg, or rHA 45μg, 15μg, 7.5μg or 3.8μg with GLA/SE. A pioneer group was monitored through Day 42 before randomizing remaining subjects. H5-specific antibody was determined by hemagglutination inhibition (HAI) and microneutralization (MN) on Days 0, 21 and 42. 392 subjects were randomized, of whom 380 (97%) received two doses and 386 (98%) completed 12 months of follow-up. Injection site pain and tenderness were seen in 50–70% of rHA+GLA/SE recipients and 4–9% of rHA alone and placebo recipients, but most complaints were mild to moderate in intensity. After two doses, the proportions of subjects with HAI titers ≥1:40 were 32% and 15% in the unadjuvanted 135μg and 45μg groups, and 82%, 75%, 66%, and 72% in those receiving 45μg, 15μg, 7.5μg, or 3.8μg with GLA/SE. The geometric mean titers (GMTs) of HAI antibody on Day 42 were 128, 95, 69, and 72 in the 45μg, 15μg, 7.5μg, or 3.8μg with GLA/SE groups, respectively. rHA GLA/SE was well tolerated and immunogenic in healthy adults, and GLA/SE substantially improved the serum antibody response. rHA expressed using BEVS recombinant DNA platform technology represents a promising strategy for pandemic control.