Safety and immunogenicity of investigational seasonal influenza hemagglutinin DNA vaccine followed by trivalent inactivated vaccine administered intradermally or intramuscularly in healthy adults: An open-label randomized phase 1 clinical trial
Autoři:
Cristina Carter aff001; Katherine V. Houser aff001; Galina V. Yamshchikov aff001; Abbie R. Bellamy aff002; Jeanine May aff002; Mary E. Enama aff001; Uzma Sarwar aff001; Brenda Larkin aff001; Robert T. Bailer aff001; Richard Koup aff001; Grace L. Chen aff001; Shital M. Patel aff003; Patricia Winokur aff004; Robert Belshe aff005; Cornelia L. Dekker aff006; Barney S. Graham aff001; Julie E. Ledgerwood aff001;
Působiště autorů:
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America
aff001; The Emmes Corporation, Rockville, MD, United States of America
aff002; Departments of Medicine and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America
aff003; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, United States of America
aff004; Division of Infectious Diseases, Allergy and Immunology, Saint Louis University, St. Louis, MO, United States of America
aff005; Department of Pediatrics (Infectious Diseases), Stanford University Medical Center, Stanford, CA, United States of America
aff006
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0222178
Souhrn
Background
Seasonal influenza results in significant morbidity and mortality worldwide, but the currently licensed inactivated vaccines generally have low vaccine efficacies and could be improved. In this phase 1 clinical trial, we compared seasonal influenza vaccine regimens with different priming strategies, prime-boost intervals, and administration routes to determine the impact of these variables on the resulting antibody response.
Methods
Between August 17, 2012 and January 25, 2013, four sites enrolled healthy adults 18–70 years of age. Subjects were randomized to receive one of the following vaccination regimens: trivalent hemagglutinin (HA) DNA prime followed by trivalent inactivated influenza vaccine (IIV3) boost with a 3.5 month interval (DNA-IIV3), IIV3 prime followed by IIV3 boost with a 10 month interval (IIV3-IIV3), or concurrent DNA and IIV3 prime followed by IIV3 boost with a 10 month interval (DNA/IIV3-IIV3). Each regimen was additionally stratified by an IIV3 administration route of either intramuscular (IM) or intradermal (ID). DNA vaccines were administered by a needle-free jet injector (Biojector). Study objectives included evaluating the safety and tolerability of each regimen and measuring the antibody response by hemagglutination inhibition (HAI).
Results
Three hundred and sixteen subjects enrolled. Local reactogenicity was mild to moderate in severity, with higher frequencies recorded following DNA vaccine administered by Biojector compared to IIV3 by either route (p <0.02 for pain, swelling, and redness) and following IIV3 by ID route compared to IM route (p <0.001 for swelling and redness). Systemic reactogenicity was similar between regimens. Though no overall differences were observed between regimens, the highest titers post boost were observed in the DNA-IIV3 group by ID route and in the IIV3-IIV3 group by IM route.
Conclusions
All vaccination regimens were found to be safe and tolerable. While there were no overall differences between regimens, the DNA-IIV3 group by ID route, and the IIV3-IIV3 group by IM route, showed higher responses compared to the other same-route regimens.
Klíčová slova:
Biology and life sciences – Antibody response – Antibodies – Vaccination and immunization – DNA vaccination – Physiology – Biochemistry – Proteins – Immune system proteins – Medicine and health sciences – Immunology – Immune response – Infectious diseases – Infectious disease control – Vaccines – Viral diseases – Influenza – Pharmacology – Routes of administration – Immune physiology – Public and occupational health – Preventive medicine – People and places – Population groupings – Age groups – Elderly
Zdroje
1. Reed C, Chaves SS, Daily Kirley P, Emerson R, Aragon D, Hancock EB, et al. Estimating influenza disease burden from population-based surveillance data in the United States. PLoS One. 2015;10(3):e0118369. doi: 10.1371/journal.pone.0118369 25738736
2. Epperson S, Blanton L, Kniss K, Mustaquim D, Steffens C, Wallis T, et al. Influenza activity—United States, 2013–14 season and composition of the 2014–15 influenza vaccines. MMWR Morb Mortal Wkly Rep. 2014;63(22):483–90. 24898165
3. Mullooly JP, Bridges CB, Thompson WW, Chen J, Weintraub E, Jackson LA, et al. Influenza- and RSV-associated hospitalizations among adults. Vaccine. 2007;25(5):846–55. 17074423
4. Molinari NA, Ortega-Sanchez IR, Messonnier ML, Thompson WW, Wortley PM, Weintraub E, et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine. 2007;25(27):5086–96. 17544181
5. Grohskopf LA, Sokolow LZ, Broder KR, Walter EB, Fry AM, Jernigan DB. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices-United States, 2018–19 Influenza Season. MMWR Recomm Rep. 2018;67(3):1–20. doi: 10.15585/mmwr.rr6703a1 30141464
6. Palache A, Oriol-Mathieu V, Abelin A, Music T, Influenza Vaccine Supply task f. Seasonal influenza vaccine dose distribution in 157 countries (2004–2011). Vaccine. 2014;32(48):6369–76. doi: 10.1016/j.vaccine.2014.07.012 25442403
7. FDA. Influenza Virus Vaccine, Quadrivalent, Types A and Types B 2019 [Available from: https://www.fda.gov/vaccines-blood-biologics/vaccines/influenza-virus-vaccine-quadrivalent-types-and-types-b.
8. Ray R, Dos Santos G, Buck PO, Claeys C, Matias G, Innis BL, et al. A review of the value of quadrivalent influenza vaccines and their potential contribution to influenza control. Hum Vaccin Immunother. 2017;13(7):1640–52. doi: 10.1080/21645515.2017.1313375 28532276
9. FDA. Approval Letter—Fluzone Intradermal 2011 [Available from: http://wayback.archive-it.org/7993/20170723030613/https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm255160.htm.
10. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12(1):36–44. doi: 10.1016/S1473-3099(11)70295-X 22032844
11. Jefferson T, Di Pietrantonj C, Al-Ansary LA, Ferroni E, Thorning S, Thomas RE. Vaccines for preventing influenza in the elderly. Cochrane Database Syst Rev. 2010(2):CD004876. doi: 10.1002/14651858.CD004876.pub3 20166072
12. Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2010(7):CD001269. doi: 10.1002/14651858.CD001269.pub4 20614424
13. Zimmerman RK, Nowalk MP, Chung J, Jackson ML, Jackson LA, Petrie JG, et al. 2014–2015 Influenza Vaccine Effectiveness in the United States by Vaccine Type. Clin Infect Dis. 2016;63(12):1564–73. doi: 10.1093/cid/ciw635 27702768
14. Houser K, Subbarao K. Influenza vaccines: challenges and solutions. Cell Host Microbe. 2015;17(3):295–300. doi: 10.1016/j.chom.2015.02.012 25766291
15. CDC. Influenza vaccines—United States, 2018–19 influenza season 2019 [Available from: https://www.cdc.gov/flu/professionals/vaccines.htm.
16. Ledgerwood JE, Graham BS. DNA vaccines: a safe and efficient platform technology for responding to emerging infectious diseases. Hum Vaccin. 2009;5(9):623–6. 19779298
17. DeZure AD, Coates EE, Hu Z, Yamshchikov GV, Zephir KL, Enama ME, et al. An avian influenza H7 DNA priming vaccine is safe and immunogenic in a randomized phase I clinical trial. npj Vaccines. 2017;2(1):15.
18. Ledgerwood JE, Hu Z, Gordon IJ, Yamshchikov G, Enama ME, Plummer S, et al. Influenza virus h5 DNA vaccination is immunogenic by intramuscular and intradermal routes in humans. Clin Vaccine Immunol. 2012;19(11):1792–7. doi: 10.1128/CVI.05663-11 22956656
19. Ledgerwood JE, Wei CJ, Hu Z, Gordon IJ, Enama ME, Hendel CS, et al. DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials. Lancet Infect Dis. 2011;11(12):916–24. doi: 10.1016/S1473-3099(11)70240-7 21975270
20. Ledgerwood JE, Zephir K, Hu Z, Wei CJ, Chang L, Enama ME, et al. Prime-boost interval matters: a randomized phase 1 study to identify the minimum interval necessary to observe the H5 DNA influenza vaccine priming effect. J Infect Dis. 2013;208(3):418–22. doi: 10.1093/infdis/jit180 23633407
21. Houser KV, Yamshchikov GV, Bellamy AR, May J, Enama ME, Sarwar U, et al. DNA vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age: A phase 1 randomized clinical trial. PLoS One. 2018;13(11):e0206837. doi: 10.1371/journal.pone.0206837 30388160
22. Ledgerwood JE, Bellamy AR, Belshe R, Bernstein DI, Edupuganti S, Patel SM, et al. DNA priming for seasonal influenza vaccine: a phase 1b double-blind randomized clinical trial. PLoS One. 2015;10(5):e0125914. doi: 10.1371/journal.pone.0125914 25950433
23. Crank MC, Gordon IJ, Yamshchikov GV, Sitar S, Hu Z, Enama ME, et al. Phase 1 study of pandemic H1 DNA vaccine in healthy adults. PLoS One. 2015;10(4):e0123969. doi: 10.1371/journal.pone.0123969 25884189
24. Gaudinski MR, Houser KV, Morabito KM, Hu Z, Yamshchikov G, Rothwell RS, et al. Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials. Lancet. 2018;391(10120):552–62. doi: 10.1016/S0140-6736(17)33105-7 29217376
25. Graham BS, Koup RA, Roederer M, Bailer RT, Enama ME, Moodie Z, et al. Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine. J Infect Dis. 2006;194(12):1650–60. doi: 10.1086/509259 17109336
26. Ledgerwood JE, Hu Z, Costner P, Yamshchikov G, Enama ME, Plummer S, et al. Phase I clinical evaluation of seasonal influenza hemagglutinin (HA) DNA vaccine prime followed by trivalent influenza inactivated vaccine (IIV3) boost. Contemp Clin Trials. 2015;44:112–8. doi: 10.1016/j.cct.2015.08.006 26275339
27. Martin JE, Louder MK, Holman LA, Gordon IJ, Enama ME, Larkin BD, et al. A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial. Vaccine. 2008;26(50):6338–43. doi: 10.1016/j.vaccine.2008.09.026 18824060
28. Martin JE, Pierson TC, Hubka S, Rucker S, Gordon IJ, Enama ME, et al. A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial. J Infect Dis. 2007;196(12):1732–40. doi: 10.1086/523650 18190252
29. Martin JE, Sullivan NJ, Enama ME, Gordon IJ, Roederer M, Koup RA, et al. A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. Clin Vaccine Immunol. 2006;13(11):1267–77. doi: 10.1128/CVI.00162-06 16988008
30. Tebas P, Roberts CC, Muthumani K, Reuschel EL, Kudchodkar SB, Zaidi FI, et al. Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine—Preliminary Report. N Engl J Med. 2017.
31. FDA. Approval Letter- Fluzone 2012 [Available from: http://wayback.archive-it.org/7993/20170723030605/https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm310580.htm.
32. FDA. Guidance for Industry: Clinical Data Needed to Support the Licensure of Seasonal Inactivated Influenza Vaccines. U. S. DHHS, FDA, CBER.; 2007.
33. Frenck RW Jr., Belshe R, Brady RC, Winokur PL, Campbell JD, Treanor J, et al. Comparison of the immunogenicity and safety of a split-virion, inactivated, trivalent influenza vaccine (Fluzone(R)) administered by intradermal and intramuscular route in healthy adults. Vaccine. 2011;29(34):5666–74. doi: 10.1016/j.vaccine.2011.06.010 21699951
34. Gorse GJ, Falsey AR, Fling JA, Poling TL, Strout CB, Tsang PH. Intradermally-administered influenza virus vaccine is safe and immunogenic in healthy adults 18–64 years of age. Vaccine. 2013;31(19):2358–65. doi: 10.1016/j.vaccine.2013.03.008 23499604
35. Gorse GJ, Falsey AR, Johnson CM, Morrison D, Fried DL, Ervin JE, et al. Safety and immunogenicity of revaccination with reduced dose intradermal and standard dose intramuscular influenza vaccines in adults 18–64 years of age. Vaccine. 2013;31(50):6034–40. doi: 10.1016/j.vaccine.2013.09.012 24055306
36. Marra F, Young F, Richardson K, Marra CA. A meta-analysis of intradermal versus intramuscular influenza vaccines: immunogenicity and adverse events. Influenza Other Respir Viruses. 2013;7(4):584–603. doi: 10.1111/irv.12000 22974174
37. McElhaney JE, Dutz JP. Better influenza vaccines for older people: what will it take? J Infect Dis. 2008;198(5):632–4. doi: 10.1086/590435 18652548
38. McElhaney JE, Xie D, Hager WD, Barry MB, Wang Y, Kleppinger A, et al. T cell responses are better correlates of vaccine protection in the elderly. J Immunol. 2006;176(10):6333–9. 16670345
39. Lee LY, Ha do LA, Simmons C, de Jong MD, Chau NV, Schumacher R, et al. Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals. J Clin Invest. 2008;118(10):3478–90. doi: 10.1172/JCI32460 18802496
40. Young F, Marra F. A systematic review of intradermal influenza vaccines. Vaccine. 2011;29(48):8788–801. doi: 10.1016/j.vaccine.2011.09.077 21968444
41. Tsang P, Gorse GJ, Strout CB, Sperling M, Greenberg DP, Ozol-Godfrey A, et al. Immunogenicity and safety of Fluzone((R)) intradermal and high-dose influenza vaccines in older adults >/ = 65 years of age: a randomized, controlled, phase II trial. Vaccine. 2014;32(21):2507–17. doi: 10.1016/j.vaccine.2013.09.074 24120672
42. DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014;371(7):635–45. doi: 10.1056/NEJMoa1315727 25119609
43. Falsey AR, Treanor JJ, Tornieporth N, Capellan J, Gorse GJ. Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. J Infect Dis. 2009;200(2):172–80. doi: 10.1086/599790 19508159
44. Kim YC, Song JM, Lipatov AS, Choi SO, Lee JW, Donis RO, et al. Increased immunogenicity of avian influenza DNA vaccine delivered to the skin using a microneedle patch. Eur J Pharm Biopharm. 2012;81(2):239–47. doi: 10.1016/j.ejpb.2012.03.010 22504442
45. Song JM, Kim YC, O E, Compans RW, Prausnitz MR, Kang SM. DNA vaccination in the skin using microneedles improves protection against influenza. Mol Ther. 2012;20(7):1472–80. doi: 10.1038/mt.2012.69 22508490
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