학술논문
Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 Clinical Trial
Document Type
Academic Journal
Author
Mulligan, Mark J.; Bernstein, David I.; Frey, Sharon; Winokur, Patricia; Rouphael, Nadine; Dickey, Michelle; Edupuganti, Srilatha; Spearman, Paul; Anderson, Edwin; Graham, Irene; Noah, Diana L.; Mangal, Brian; Kim, Sonnie; Hill, Heather; 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
Source
Open Forum Infectious Diseases. Dec 01, 2014 1(3)
Subject
Language
English
ISSN
2328-8957
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.