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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.

AbstractBACKGROUND:
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).
METHODS:
Healthy adults 18-49 were randomized to two IM doses on Days 0 and 21 of placebo; unadjuvanted rHA 135 μg or 45 μg, or rHA 45 μg, 15 μg, 7.5 μg or 3.8 μg 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.
RESULTS:
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 135 μg and 45 μg groups, and 82%, 75%, 66%, and 72% in those receiving 45 μg, 15 μg, 7.5 μg, or 3.8 μg with GLA/SE. The geometric mean titers (GMTs) of HAI antibody on Day 42 were 128, 95, 69, and 72 in the 45 μg, 15 μg, 7.5 μg, or 3.8 μg with GLA/SE groups, respectively.
CONCLUSIONS:
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.
AuthorsJohn J Treanor, Brandon Essink, Steven Hull, Steven Reed, Ruvim Izikson, Peter Patriarca, Karen L Goldenthal, Robert Kohberger, Lisa M Dunkle
JournalVaccine (Vaccine) Vol. 31 Issue 48 Pg. 5760-5 (Nov 19 2013) ISSN: 1873-2518 [Electronic] Netherlands
PMID24075920 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2013. Published by Elsevier Ltd.
Chemical References
  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Emulsions
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Lipid A
  • Placebos
  • Recombinant Proteins
  • Vaccines, Synthetic
  • hemagglutinin, avian influenza A virus
Topics
  • Adjuvants, Immunologic (administration & dosage, adverse effects)
  • Adolescent
  • Adult
  • Animals
  • Antibodies, Viral (blood)
  • Drug-Related Side Effects and Adverse Reactions (epidemiology, pathology)
  • Emulsions (administration & dosage, adverse effects)
  • Female
  • Healthy Volunteers
  • Hemagglutination Inhibition Tests
  • Hemagglutinin Glycoproteins, Influenza Virus (genetics, immunology)
  • Humans
  • Influenza Vaccines (administration & dosage, adverse effects, immunology)
  • Lipid A (administration & dosage, adverse effects, analogs & derivatives)
  • Male
  • Middle Aged
  • Placebos (administration & dosage)
  • Recombinant Proteins (genetics, immunology)
  • Vaccines, Synthetic (administration & dosage, adverse effects, immunology)
  • Young Adult

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