RESUMEN
BACKGROUND: The efficacy of current influenza vaccines is limited in vulnerable populations. DNA vaccines can be produced rapidly, and may offer a potential strategy to improve vaccine immunogenicity, indicated by studies with H5 influenza DNA vaccine prime followed by inactivated vaccine boost. METHODS: Four sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza DNA vaccine prime (n=65) or phosphate buffered saline (PBS) (n=66) administered intramuscularly with Biojector. All subjects received the 2012/13 seasonal inactivated influenza vaccine, trivalent (IIV3) 36 weeks after the priming injection. Vaccine safety and tolerability was the primary objective and measurement of antibody response by hemagglutination inhibition (HAI) was the secondary objective. RESULTS: The DNA vaccine prime-IIV3 boost regimen was safe and well tolerated. Significant differences in HAI responses between the DNA vaccine prime and the PBS prime groups were not detected in this study. CONCLUSION: While DNA priming significantly improved the response to a conventional monovalent H5 vaccine in a previous study, it was not effective in adults using seasonal influenza strains, possibly due to pre-existing immunity to the prime, unmatched prime and boost antigens, or the lengthy 36 week boost interval. Careful optimization of the DNA prime-IIV3 boost regimen as related to antigen matching, interval between vaccinations, and pre-existing immune responses to influenza is likely to be needed in further evaluations of this vaccine strategy. In particular, testing this concept in younger age groups with less prior exposure to seasonal influenza strains may be informative. TRIAL REGISTRATION: ClinicalTrials.gov NCT01498718.
Asunto(s)
Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Vacunas de ADN/administración & dosificación , Vacunas de Productos Inactivados/administración & dosificación , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Subtipo H5N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/inmunología , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Vacunas de ADN/efectos adversos , Vacunas de ADN/inmunología , Vacunas de Productos Inactivados/inmunología , Adulto JovenRESUMEN
The ongoing epidemic of Ebola virus in West Africa and attendant cases described in other parts of the world has focused attention on this heretofore rare disease. In this brief opinion article, we provide a short primer on the epidemiology, pathogenesis, clinical manifestations, US-based hospital preparedness, vaccine and therapy development, and control of Ebola virus disease for noninfectious disease physicians.