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

• Published in: PloS one Vol. 14; no. 9; p. e0222178
• Main Authors: Carter, Cristina, Houser, Katherine V., Yamshchikov, Galina V., Bellamy, Abbie R., May, Jeanine, Enama, Mary E., Sarwar, Uzma, Larkin, Brenda, Bailer, Robert T., Koup, Richard, Chen, Grace L., Patel, Shital M., Winokur, Patricia, Belshe, Robert, Dekker, Cornelia L., Graham, Barney S., Ledgerwood, Julie E.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.09.2019; Public Library of Science (PLoS)
• Subjects: Administration, Intranasal; Adult; Adults; Age; Aged; Analysis; Antibodies; Antibody response; Biology and Life Sciences; Clinical trials; Deoxyribonucleic acid; DNA; DNA vaccines; Drug dosages; Female; Free jets; Genetic research; Health aspects; Healthy Volunteers; Hemagglutination inhibition; Hemagglutinins; Hemagglutinins - administration & dosage; Hemagglutinins - adverse effects; Hemagglutinins - immunology; Humans; Immunization; Immunization, Secondary; Immunogenicity; Infections; Infectious diseases; Influenza; Influenza vaccines; Influenza Vaccines - administration & dosage; Influenza Vaccines - adverse effects; Influenza Vaccines - immunology; Influenza, Human - prevention & control; Injections, Intradermal; Lectins; Male; Medical schools; Medicine; Medicine and Health Sciences; Middle Aged; Morbidity; Mortality; Older people; Pain; Patient outcomes; People and Places; Prevention; Priming; Randomization; Risk factors; Route selection; Safety; Safety and security measures; Swelling; Systematic review; Vaccination; Vaccine efficacy; Vaccines; Vaccines, DNA - administration & dosage; Vaccines, DNA - adverse effects; Vaccines, DNA - immunology; Vaccines, Inactivated - administration & dosage; Vaccines, Inactivated - adverse effects; Vaccines, Inactivated - immunology; Young Adult; Zika virus; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0222178

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. 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). 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. 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.