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

English version

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
prolekare.web.journal.doi_sk: 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 – Biochemistry – Proteins – People and places – Population groupings – Medicine and health sciences – Physiology – Pharmacology – Infectious diseases – Immunology – Immune response – Immune physiology – Vaccination and immunization – Public and occupational health – Preventive medicine – Immune system proteins – Infectious disease control – Vaccines – Antibodies – Age groups – Viral diseases – Elderly – Antibody response – Influenza – DNA vaccination – Routes of administration

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