Serological responses to an avian influenza A/H7N9 vaccine mixed at the point-of-use with MF59 adjuvant a randomized clinical trial

Mark J. Mulligan, David I. Bernstein, Patricia Winokur, Richard Rupp, Evan Anderson, Nadine Rouphael, Michelle Dickey, Jack T. Stapleton, Srilatha Edupuganti, Paul Spearman, Dilek Ince, Diana L. Noah, Heather Hill, Abbie R. Bellamy, Karen Mask, Allison Beck, Lilin Lai, Nayoka Rimann, Colleen Kelley, Melinda OgilvieEileen Osinski, Dawn Battle, Andres Camacho-Gonzalez, Anita McElroy, Andi Shane, Larry Anderson, Kathy Stephens, Brooke Hartwell, Teresa Ball, Laila Hussani, Theda Gibson, Melanie Johnson, Bethany Sederdahl, Natasha Mann, Robert Frenck, Rebecca Brady, Tara Foltz, Amy Cline, Sarah McCartney, Margery Huron, Jeffrey Meier, Margo Schilling, Nancy Wagner, Geraldine Dull, Kathy Flanders, Dan Zhao, Mary Reidy, Gretchen Cress, Nikki Gerot, Diane Barrett, Carrie Harrington, Amy McMahan, Marianne Shafer, Lori Simon, Barbara Taggart, Valerie Johnson, Donna Bowen, Shixiong Li, Candi Looney, Megan May, Rachel May, Lawanda Parker, Bridgette Myers, Nertaissa Cochran, Michelle Bell, Logan Haller, Claire Stablein, Sara Marshall, Megan McDonough, Fenhua He, Kuo Guo, Linda Lambert, Wendy Buchanan, Valerie Riddle, Suzanne Murray, Richard Gorman

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

RESULTS Hemagglutination inhibition antibodies were minimal after participants received an unadjuvanted vaccine. After receiving 2 doses of H7N9 vaccine at a dosage of 3.75 μg plus the MF59 adjuvant, day 42 seroconversion occurred in 58 participants (59%; 95%CI, 48%-68%). The peak seroconversion occurred at day 29 in 62 participants (62%; 95%CI, 52%-72%). The day 42 geometric mean titer was 33.0 (95%CI, 24.7-44.1). Higher antigen doses were not associated with increased response. For the neutralizing antibody assays, after receiving 3.75 μg of H7N9 vaccine plus the MF59 adjuvant, day 42 seroconversion occurred in 81 participants (82%; 95%CI, 73%-89%). The day 42 geometric mean titer was 81.4 (95%CI, 66.6-99.5). There was no statistically significant difference in day 42 hemagglutination inhibition seroconversion after mixing adjuvant with either the first or both 15 μg doses (n = 34 [35%; 95%CI, 25%-45%] vs n = 47 [47%; 95%CI, 37%-58%], respectively; P = .10). Recent receipt of seasonal influenza vaccination and older age were associated with attenuated response. No vaccine-related serious adverse events occurred. Solicited postvaccination symptoms were generally mild with more local symptoms seen in participants who received the adjuvant.

CONCLUSIONS AND RELEVANCE Point-of-use mixing and administration of 2 doses of H7N9 vaccine at the lowest tested antigen dose with MF59 adjuvant produced seroconversion in 59%of participants. Although these findings indicate potential value in this approach, the study is limited by the absence of antibody data beyond 42 days and the absence of clinical outcomes.

TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01938742.

DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, double-blind, phase 2 trial at 4 US sites enrolled 700 adults aged 19 to 64 years beginning in September 2013; 6-month follow-up was completed in May 2014.

IMPORTANCE Human infections with avian influenza A/H7N9 have resulted in high morbidity and mortality in China.

OBJECTIVE To compare safety and immunogenicity of different doses of influenza A/Shanghai/2/13 (H7N9) vaccine mixed with or without the MF59 adjuvant.

INTERVENTIONS The H7N9 inactivated virus vaccine was administered intramuscularly on days 0 and 21 at nominal doses of 3.75, 7.5, 15, or 45 μg of hemagglutinin (actual doses approximately 50% higher) with or without the MF59 adjuvant. A total 99, 100, or 101 participants were randomized to each group (7 groups; N = 700).

MAIN OUTCOMES AND MEASURES Proportions achieving day 42 antibody titer of 40 or greater or seroconversion (a minimum 4-fold increase to titer-40) with the hemagglutination inhibition assay; vaccine-related serious adverse events through month 13; and solicited postvaccination symptoms through day 7.

Original languageEnglish (US)
Pages (from-to)1409-1419
Number of pages11
JournalJAMA - Journal of the American Medical Association
Volume312
Issue number14
DOIs
StatePublished - Oct 8 2014

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Serological responses to an avian influenza A/H7N9 vaccine mixed at the point-of-use with MF59 adjuvant a randomized clinical trial'. Together they form a unique fingerprint.

  • Cite this

    Mulligan, M. J., Bernstein, D. I., Winokur, P., Rupp, R., Anderson, E., Rouphael, N., Dickey, M., Stapleton, J. T., Edupuganti, S., Spearman, P., Ince, D., Noah, D. L., Hill, H., Bellamy, A. R., Mask, K., Beck, A., Lai, L., Rimann, N., Kelley, C., ... Gorman, R. (2014). Serological responses to an avian influenza A/H7N9 vaccine mixed at the point-of-use with MF59 adjuvant a randomized clinical trial. JAMA - Journal of the American Medical Association, 312(14), 1409-1419. https://doi.org/10.1001/jama.2014.12854