DNA vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age: A phase 1 randomized clinical trial

• Authors: Katherine V. Houser, National Institute of Allergy and Infectious Diseases; Galina V. Yamshchikov, National Institute of Allergy and Infectious Diseases; Abbie R. Bellamy, Emmes Corporation; Jeanine May, Emmes Corporation; Mary E. Enama, National Institute of Allergy and Infectious Diseases; Uzma Sarwar, National Institute of Allergy and Infectious Diseases; Brenda Larkin, National Institute of Allergy and Infectious Diseases; Robert T. Bailer, National Institute of Allergy and Infectious Diseases; Richard Koup, National Institute of Allergy and Infectious Diseases; Myeisha Paskel, National Institute of Allergy and Infectious Diseases; Kanta Subbarao, National Institute of Allergy and Infectious Diseases; Edwin Anderson, St Louis University; David I. Bernstein, University of Cincinnati; Buddy Creech, Vanderbilt University; Harry Keyserling, Emory University; Paul Spearman, Emory University; Peter F. Wright, Dartmouth College; Barney S. Graham, National Institute of Allergy and Infectious Diseases; Julie E. Ledgerwood, National Institute of Allergy and Infectious Diseases
• Journal Title: PLoS ONE
• Volume: Volume 13, Number 11
• Publisher: Public Library of Science | 2018-11-02, Pages e0206837-e0206837
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1371/journal.pone.0206837
• Subjects: Health Sciences, Immunology; Health Sciences, Public Health
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; NEUTRALIZING ANTIBODY; HEALTHY-ADULTS; DISEASE; VIRUS; BURDEN; SAFE

Abstract

BACKGROUND: Children are susceptible to severe influenza infections and facilitate community transmission. One potential strategy to improve vaccine immunogenicity in children against seasonal influenza involves a trivalent hemagglutinin DNA prime-trivalent inactivated influenza vaccine (IIV3) boost regimen. METHODS: Sites enrolled adolescents, followed by younger children, to receive DNA prime (1 mg or 4 mg) intramuscularly by needle-free jet injector (Biojector), followed by split virus 2012/13 seasonal IIV3 boost by needle and syringe approximately 18 weeks later. A comparator group received IIV3 prime and boost at similar intervals. Primary study objectives included evaluation of the safety and tolerability of the vaccine regimens, with secondary objectives of measuring antibody responses at four weeks post boost by hemagglutination inhibition (HAI) and neutralization assays. RESULTS: Seventy-five children ≥6 to ≤17 years old enrolled. Local reactogenicity was higher after DNA prime compared to IIV3 prime (p<0.001 for pain/tenderness, redness, or swelling), but symptoms were mild to moderate in severity. Systemic reactogenicity was similar between vaccines. Overall, antibody responses were similar among groups, although HAI antibodies revealed a trend towards higher responses following 4 mg DNA-IIV3 compared to IIV3-IIV3. The fold increase of HAI antibodies to A/California/07/2009 [A(H1N1)pdm09] was significantly greater following 4 mg DNA-IIV3 (10.12 fold, 5.60-18.27 95%CI) compared to IIV3-IIV3 (3.86 fold, 2.32-6.44 95%CI). Similar neutralizing titers were observed between regimens, with a trend towards increased response frequencies in 4 mg DNA-IIV3. However, significant differences in fold increase, reported as geometric mean fold ratios, were detected against the H1N1 viruses within the neutralization panel: A/New Caledonia/20/1999 (1.41 fold, 1.10-1.81 95%CI) and A/South Carolina/1/1918 (1.55 fold, 1.27-1.89 95%CI). CONCLUSIONS: In this first pediatric DNA vaccine study conducted in the U.S., the DNA prime-IIV3 boost regimen was safe and well tolerated. In children, the 4 mg DNA-IIV3 regimen resulted in antibody responses comparable to the IIV3-IIV3 regimen.