Patricia Winokur1, Hana M El Sahly2, Mark J Mulligan3, Sharon E Frey4, Richard Rupp5, Evan J Anderson6, Kathryn M Edwards7, David I Bernstein8, Kenneth Schmader9, Lisa A Jackson10, Wilbur H Chen11, Heather Hill12, Abigail Bellamy12. 1. Division of Infectious Diseases, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States. Electronic address: patricia-winokur@uiowa.edu. 2. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States. 3. The Hope Clinic of the Emory Vaccine Center, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States. 4. Department of Medicine, Saint Louis University School of Medicine, Saint Louis, MO, United States. 5. Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, United States. 6. Emory Children's Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States. 7. Department of Pediatrics, Vanderbilt Vaccine Research Program, Vanderbilt University, Nashville, TN, United States. 8. Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, United States. 9. Duke University, United States. 10. Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States. 11. Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, United States. 12. The Emmes Corporation, Rockville, MD, United States.
Abstract
BACKGROUND: The number of human influenza A (H7N9) infections has escalated since 2013 with high resultant mortality. We conducted a phase II, randomized, partially-blinded trial to evaluate the safety and immunogenicity of an MF59-adjuvanted inactivated, split virion, H7N9 influenza vaccine (H7N9 IIV) administered at various dose levels and schedules in older adults. METHODS: 479 adults ≥ 65 years of age in stable health were randomized to one of six groups to receive either 3.75, 7.5 or 15 µg of influenza A/Shanghai/02/2013 (H7N9) IIV adjuvanted with MF59 given as a 3-dose series either on days 1, 28 and 168 or on days 1, 57 and 168. Immunogenicity was assessed using both hemagglutination inhibition (HAI) and microneutralization (MN) assays prior to and 28 days following each dose. Safety was assessed through 1 year following the last dose. RESULTS: Subjects in all groups had only modest immune responses, with the HAI GMT < 20 after the second vaccine dose and <29 after the third vaccine dose. HAI titers ≥ 40 were seen in <37% of subjects after the second dose and <49% after the third dose. There were no significant differences seen between the two dose schedules. MN titers followed similar patterns, although the titers were approximately two-fold higher than the HAI titers. Logistic regression modeling demonstrated no statistically significant associations between the immune responses and age, sex or body mass index whereas recent prior receipt of seasonal influenza vaccine significantly reduced the HAI response [OR 0.13 (95% CI 0.05, 0.33); p < 0.001]. Overall, the vaccine was well tolerated. Two mild potentially immune mediated adverse events occurred, lichen planus and guttate psoriasis. CONCLUSIONS: MF59-adjuvanted H7N9 IIV was only modestly immunogenic in the older adult population following three doses. There were no significant differences in antibody responses noted among the various antigen doses or the two dose schedules.
BACKGROUND: The number of human influenza A (H7N9) infections has escalated since 2013 with high resultant mortality. We conducted a phase II, randomized, partially-blinded trial to evaluate the safety and immunogenicity of an MF59-adjuvanted inactivated, split virion, H7N9 influenza vaccine (H7N9 IIV) administered at various dose levels and schedules in older adults. METHODS: 479 adults ≥ 65 years of age in stable health were randomized to one of six groups to receive either 3.75, 7.5 or 15 µg of influenza A/Shanghai/02/2013 (H7N9) IIV adjuvanted with MF59 given as a 3-dose series either on days 1, 28 and 168 or on days 1, 57 and 168. Immunogenicity was assessed using both hemagglutination inhibition (HAI) and microneutralization (MN) assays prior to and 28 days following each dose. Safety was assessed through 1 year following the last dose. RESULTS: Subjects in all groups had only modest immune responses, with the HAI GMT < 20 after the second vaccine dose and <29 after the third vaccine dose. HAI titers ≥ 40 were seen in <37% of subjects after the second dose and <49% after the third dose. There were no significant differences seen between the two dose schedules. MN titers followed similar patterns, although the titers were approximately two-fold higher than the HAI titers. Logistic regression modeling demonstrated no statistically significant associations between the immune responses and age, sex or body mass index whereas recent prior receipt of seasonal influenza vaccine significantly reduced the HAI response [OR 0.13 (95% CI 0.05, 0.33); p < 0.001]. Overall, the vaccine was well tolerated. Two mild potentially immune mediated adverse events occurred, lichen planus and guttate psoriasis. CONCLUSIONS: MF59-adjuvanted H7N9 IIV was only modestly immunogenic in the older adult population following three doses. There were no significant differences in antibody responses noted among the various antigen doses or the two dose schedules.
Authors: A M Palache; W E Beyer; M J Sprenger; N Masurel; S de Jonge; A Vardy; B Charpentier; J Noury; W C van Beek; R J Borst Journal: Vaccine Date: 1993 Impact factor: 3.641
Authors: Gui-Mei Li; Christopher Chiu; Jens Wrammert; Megan McCausland; Sarah F Andrews; Nai-Ying Zheng; Jane-Hwei Lee; Min Huang; Xinyan Qu; Srilatha Edupuganti; Mark Mulligan; Suman R Das; Jonathan W Yewdell; Aneesh K Mehta; Patrick C Wilson; Rafi Ahmed Journal: Proc Natl Acad Sci U S A Date: 2012-05-21 Impact factor: 11.205