Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 Clinical Trial
Author:
Mulligan Mark J.1, Bernstein David I.2, Frey Sharon3, Winokur Patricia4, Rouphael Nadine1, Dickey Michelle2, Edupuganti Srilatha1, Spearman Paul5, Anderson Edwin3, Graham Irene3, Noah Diana L.6, Mangal Brian7, Kim Sonnie8, Hill Heather7, Whitaker Jenifer, Emery William, Beck Allison, Stephens Kathy, Hartwell Brooke, Ogilvie Melinda, Rimann Nayoka, Osinski Eileen, Destefano Ellen, Gajadhar Theda, Strudwick Amanda, Pierce Karen, Lai Lilin, Yue Ling, Wang Dongli, Ying Carl, Cline Amy, Foltz Tara, Wagner Nancy, Dull Geraldine, Pacatte Thomas, Taggart Barbara, Johnson Valerie, Haller Logan, Looney Candi, Li Shixiong, May Megan, Myers Bridgette, May Rachel, Parker Lawanda, Cochran Nertaissa, Bowen Donna, Bell Michelle, Scoggins Jeffery, Burns Angela, Stablein Claire, Wolff Mark, Jolles Bernadette, Leung Brenda, Lambert Linda, Shorer Shy, Buchanan Wendy, Murray Suzanne, Chang Soju, Gorman Richard
Affiliation:
1. Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, Georgia 2. Cincinnati Children's Hospital Medical Center, University of Cincinnati, Ohio 3. Division of Infectious Diseases and Immunology, Saint Louis University, Missouri 4. Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City 5. Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia 6. Southern Research Institute, Birmingham, Alabama 7. EMMES Corporation, Rockville, Maryland 8. Division of Microbiology and Infectious Diseases/National Institute of Allergy and Infection Diseases/National Institutes of Health, Viral Respiratory Diseases Section, Respiratory Diseases Branch, Bethesda, Maryland
Abstract
Abstract
Background. Avian influenza A/H5N1 has threatened human health for nearly 2 decades. Avian influenza A vaccine without adjuvant is poorly immunogenic. A flexible rapid tactic for mass vaccination will be needed if a pandemic occurs.
Methods. A multicenter, randomized, blinded phase 1 clinical trial evaluated safety and antibody responses after point-of-use mixing of influenza A/Indonesia/05/2005 (H5N1) vaccine with MF59 adjuvant. Field-site pharmacies mixed 3.75, 7.5, or 15 mcg of antigen with or without MF59 adjuvant just prior to intramuscular administration on days 0 and 21 of healthy adults aged 18–49 years.
Results. Two hundred and seventy subjects were enrolled. After vaccination, titers of hemagglutination inhibition antibody ≥1:40 were achieved in 80% of subjects receiving 3.75 mcg + MF59 vs only 14% receiving 15 mcg without adjuvant (P < .0001). Peak hemagglutination inhibition antibody geometric mean titers for vaccine + MF59 were ∼65 regardless of antigen dose, and neutralizing titers were 2- to 3-fold higher. Vaccine + MF59 produced cross-reactive antibody responses against 4 heterologous H5N1 viruses. Excellent safety and tolerability were demonstrated.
Conclusions. Point-of-use mixing of H5N1 antigen and MF59 adjuvant achieved target antibody titers in a high percentage of subjects and was safe. The feasibility of the point-of-use mixing should be studied further.
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Oncology
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