Journal Article

Stable emulsion (SE) alone is an effective adjuvant for a recombinant, baculovirus-expressed H5 influenza vaccine in healthy adults: A Phase 2 trial

Izikson, Ruvim, Muse, Derek, El Sahly, Hana M., Goldenthal, Karen L., Treanor, John J., Patriarca, Peter, Chu, Laurence, Essink, Brandon, Dunkle, Lisa M.

2017

Overview

Influenza A viruses of the H5 subtype have been identified as important targets for development of vaccines. Achievement of potentially protective antibody responses against pandemic strains has usually required the use of adjuvants. We evaluated a candidate A/Indonesia/05/2005 (H5) vaccine generated by baculovirus expression of recombinant hemagglutinin (HA) protein with or without stable emulsion (SE) as an adjuvant. Healthy subjects 18–49years old were randomized (1:1:1:1) to receive two doses of rHA at 7.5ug per dose (no adjuvant), or 3.8ug, 7.5ug, or 15ug per dose formulated with 2% SE separated by 21days, and serum from day 0, 21, 42, and 201 assessed by hemagglutination-inhibition. 341 subjects were enrolled in the study and 321 received two doses of vaccine. Vaccination was well tolerated in all groups. After two doses, seroconversion was noted in only 9% (95% confidence interval 4%, 17%) of recipients of unadjuvanted vaccine at 7.5ug, but in 70% (59%, 80%), 76% (65%, 85%), and 83% (73%, 91%) of those receiving adjuvanted vaccine at 3.8ug, 7.5ug, or 15ug respectively. Stable emulsion alone is an effective adjuvant for rH5 vaccine in healthy adults. All three adjuvanted dose groups met the current criterion for seroconversion rate for pandemic vaccines. This dose-ranging study also identified a group (15ug per dose formulated with 2% SE) that met the criteria for both seroconversion and percentage of subjects achieving an HI antibody titer⩾40. These Phase 2 data support the further clinical development of SE adjuvanted Panblok H5. Clinical trial registration: NCT01612000. The protocol was approved by the relevant Institutional Review Board for each study site, and the study was conducted in accordance with the Declaration of Helsinki, International Conference of Harmonisation – Good Clinical Practice, and all applicable laws and regulations. All participants provided written informed consent before study procedures.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adjuvant / adjuvants / Adjuvants, Immunologic - administration & dosage / Adjuvants, Immunologic - chemistry / Adolescent / Adult / adults / Allergy and Immunology / antibodies / Antibodies, Viral - biosynthesis / Avian flu / Baculoviridae / Baculoviridae - genetics / Baculoviridae - immunology / blood serum / confidence interval / Dose-Response Relationship, Immunologic / Emulsions / Female / Health care / Hemagglutination Inhibition Tests / Hemagglutinin Glycoproteins, Influenza Virus - genetics / Hemagglutinin Glycoproteins, Influenza Virus - immunology / hemagglutinins / Humans / Immunization / Immunization Schedule / Influenza / Influenza A virus / Influenza A Virus, H5N1 Subtype - drug effects / Influenza A Virus, H5N1 Subtype - growth & development / Influenza A Virus, H5N1 Subtype - immunology / Influenza Vaccines - administration & dosage / Influenza Vaccines - biosynthesis / Influenza Vaccines - genetics / Influenza, Human - immunology / Influenza, Human - prevention & control / Influenza, Human - virology / laws and regulations / Male / Middle Aged / Pain / Pandemic / Pandemics / Recombinant HA / seroconversion / vaccination / Vaccine / vaccine development / Vaccines / Vaccines, Synthetic / Viruses