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Mulligan MJ, Bernstein DI, Frey S, et al. Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 Clinical Trial. Open Forum Infect Dis. 2014;1(3):ofu102doi: 10.1093/ofid/ofu102.
Mulligan, M. J., Bernstein, D. I., Frey, S., Winokur, P., Rouphael, N., Dickey, M., Edupuganti, S., Spearman, P., Anderson, E., Graham, I., Noah, D. L., Mangal, B., Kim, S., Hill, H., Whitaker, J., Emery, W., Beck, A., Stephens, K., Hartwell, B., Ogilvie, M., Rimann, N., Osinski, E., Destefano, E., Gajadhar, T., Strudwick, A., Pierce, K., Lai, L., Yue, L., Wang, D., Ying, C., Cline, A., Foltz, T., Wagner, N., Dull, G., Pacatte, T., Taggart, B., Johnson, V., Haller, L., Looney, C., Li, S., May, M., Myers, B., May, R., Parker, L., Cochran, N., Bowen, D., Bell, M., Scoggins, J., Burns, A., Stablein, C., Wolff, M., Jolles, B., Leung, B., Lambert, L., Shorer, S., Buchanan, W., Murray, S., Chang, S., & Gorman, R. (2014). Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 Clinical Trial. Open forum infectious diseases, 1(3), ofu102. https://doi.org/10.1093/ofid/ofu102
Mulligan, Mark J, et al. "Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 Clinical Trial." Open forum infectious diseases vol. 1,3 (2014): ofu102. doi: https://doi.org/10.1093/ofid/ofu102
Mulligan MJ, Bernstein DI, Frey S, Winokur P, Rouphael N, Dickey M, Edupuganti S, Spearman P, Anderson E, Graham I, Noah DL, Mangal B, Kim S, Hill H, Whitaker J, Emery W, Beck A, Stephens K, Hartwell B, Ogilvie M, Rimann N, Osinski E, Destefano E, Gajadhar T, Strudwick A, Pierce K, Lai L, Yue L, Wang D, Ying C, Cline A, Foltz T, Wagner N, Dull G, Pacatte T, Taggart B, Johnson V, Haller L, Looney C, Li S, May M, Myers B, May R, Parker L, Cochran N, Bowen D, Bell M, Scoggins J, Burns A, Stablein C, Wolff M, Jolles B, Leung B, Lambert L, Shorer S, Buchanan W, Murray S, Chang S, Gorman R. Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 Clinical Trial. Open Forum Infect Dis. 2014 Nov 18;1(3):ofu102. doi: 10.1093/ofid/ofu102. eCollection 2014 Dec. PMID: 25734170; PMCID: PMC4324215.
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Open Forum Infect Dis. 2014 Nov 18;1(3):ofu102. doi: 10.1093/ofid/ofu102. eCollection 2014 Dec.

Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 Clinical Trial.

Open forum infectious diseases

Mark J Mulligan, David I Bernstein, Sharon Frey, Patricia Winokur, Nadine Rouphael, Michelle Dickey, Srilatha Edupuganti, Paul Spearman, Edwin Anderson, Irene Graham, Diana L Noah, Brian Mangal, Sonnie Kim, Heather Hill, Jenifer Whitaker, William Emery, Allison Beck, Kathy Stephens, Brooke Hartwell, Melinda Ogilvie, Nayoka Rimann, Eileen Osinski, Ellen Destefano, Theda Gajadhar, Amanda Strudwick, Karen Pierce, Lilin Lai, Ling Yue, Dongli Wang, Carl Ying, Amy Cline, Tara Foltz, Nancy Wagner, Geraldine Dull, Thomas Pacatte, Barbara Taggart, Valerie Johnson, Logan Haller, Candi Looney, Shixiong Li, Megan May, Bridgette Myers, Rachel May, Lawanda Parker, Nertaissa Cochran, Donna Bowen, Michelle Bell, Jeffery Scoggins, Angela Burns, Claire Stablein, Mark Wolff, Bernadette Jolles, Brenda Leung, Linda Lambert, Shy Shorer, Wendy Buchanan, Suzanne Murray, Soju Chang, Richard Gorman

Affiliations

  1. Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.

PMID: 25734170 PMCID: PMC4324215 DOI: 10.1093/ofid/ofu102

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.

Keywords: H5N1; MF59; adjuvant; antibody; avian influenza; pandemic preparedness; point-of-use mixing; vaccine

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