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

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• 作者：John J. Treanor ; Br ; on Essink ; Steven Hull ; Steven Reed ; Ruvim Izikson ; Peter Patriarca ; Karen L. Goldenthal ; Robert Kohberger ; Lisa M. Dunkle
• 关键词：Pandemic influenza ; Vaccines ; Adjuvants ; H5N1
• 刊名：Vaccine
• 出版年：19 November, 2013
• 年：2013
• 卷：31
• 期：48
• 页码：5760-5765
• 全文大小：605 K

文摘

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 135 渭g or 45 渭g, or rHA 45 渭g, 15 渭g, 7.5 渭g or 3.8 渭g 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 鈮?:40 were 32% and 15% in the unadjuvanted 135 渭g and 45 渭g groups, and 82%, 75%, 66%, and 72% in those receiving 45 渭g, 15 渭g, 7.5 渭g, or 3.8 渭g with GLA/SE. The geometric mean titers (GMTs) of HAI antibody on Day 42 were 128, 95, 69, and 72 in the 45 渭g, 15 渭g, 7.5 渭g, or 3.8 渭g 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.