John J Treanor1, Laurence Chu2, Brandon Essink3, Derek Muse4, Hana M El Sahly5, Ruvim Izikson6, Karen L Goldenthal7, Peter Patriarca8, Lisa M Dunkle6. 1. University of Rochester Medical Center, Rochester, NY, United States. Electronic address: John_Treanor@UMRC.Rochester.edu. 2. Benchmark Research, Austin, TX, United States. 3. Meridian Clinical Research, Omaha, NE, United States. 4. Jean Brown Research, Salt Lake City, UT, United States. 5. Baylor College of Medicine, Houston, TX, United States. 6. Protein Sciences Corporation, Meriden, CT, United States. 7. Independent Consultant, Bethesda, MD, United States. 8. Biologics Consulting Group, Bethesda, MD, United States.
Abstract
BACKGROUND: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. OBJECTIVES: 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. METHODS: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. RESULTS:341 subjects were enrolled in the study and 321 received two doses ofvaccine. 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. CONCLUSIONS: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.
RCT Entities:
BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Tazio Vanni; Beatriz C Thomé; Erin Sparrow; Martin Friede; Christopher B Fox; Anna Marie Beckmann; Chuong Huynh; Gabriella Mondini; Daniela H Silveira; Juliana Y K Viscondi; Patrícia Emilia Braga; Anderson da Silva; Maria da Graça Salomão; Roberta O Piorelli; Joane P Santos; Vera Lúcia Gattás; Maria Beatriz B Lucchesi; Mayra M M de Oliveira; Marcelo E Koike; Esper G Kallas; Lucia M A Campos; Eduardo B Coelho; Marilda A M Siqueira; Cristiana C Garcia; Milene Dias Miranda; Terezinha M Paiva; Maria do Carmo S T Timenetsky; Eduardo A Adami; Milena A Akamatsu; Paulo Lee Ho; Alexander R Precioso Journal: PLoS One Date: 2022-10-18 Impact factor: 3.752
Authors: Tony Phan; Christian Devine; Erik D Laursen; Adrian Simpson; Aaron Kahn; Amit P Khandhar; Steven Mesite; Brad Besse; Ken J Mabery; Elizabeth I Flanagan; Christopher B Fox Journal: Pharmaceuticals (Basel) Date: 2020-07-28