tetano
Editor, Senior Moderator
Vaccine. 2013 Sep 26. pii: S0264-410X(13)01176-6. doi: 10.1016/j.vaccine.2013.08.064. [Epub ahead of print]
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.
Treanor JJ, Essink B, Hull S, Reed S, Izikson R, Patriarca P, Goldenthal KL, Kohberger R, Dunkle LM.
Source
University of Rochester School of Medicine, Rochester, NY, United States. Electronic address: john_treanor@urmc.rochester.edu.
Abstract
BACKGROUND:
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 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.
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 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.
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.
Copyright ? 2013. Published by Elsevier Ltd.
KEYWORDS:
Adjuvants, H5N1, Pandemic influenza, Vaccines
PMID:
24075920
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24075920
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.
Treanor JJ, Essink B, Hull S, Reed S, Izikson R, Patriarca P, Goldenthal KL, Kohberger R, Dunkle LM.
Source
University of Rochester School of Medicine, Rochester, NY, United States. Electronic address: john_treanor@urmc.rochester.edu.
Abstract
BACKGROUND:
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 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.
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 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.
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.
Copyright ? 2013. Published by Elsevier Ltd.
KEYWORDS:
Adjuvants, H5N1, Pandemic influenza, Vaccines
PMID:
24075920
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24075920