Ledgerwood Julie E, Bellamy Abbie R, Belshe Robert, Bernstein David I, Edupuganti Srilatha, Patel Shital M, Renehan Phyllis, Zajdowicz Thad, Schwartz Richard, Koup Richard, Bailer Robert T, Yamshchikov Galina V, Enama Mary E, Sarwar Uzma, Larkin Brenda, Graham Barney S
Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
The EMMES Corporation, Rockville, Maryland, United States of America.
PLoS One. 2015 May 7;10(5):e0125914. doi: 10.1371/journal.pone.0125914. eCollection 2015.
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.
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.
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.
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.
ClinicalTrials.gov NCT01498718.
目前的流感疫苗在易感人群中的效果有限。DNA疫苗能够快速生产，并且可能提供一种提高疫苗免疫原性的潜在策略，H5流感DNA疫苗初免后用灭活疫苗加强的研究表明了这一点。
四个研究点招募了健康成年人，随机分为接受2011/12季节性流感DNA疫苗初免组（n = 65）或用Biojector肌肉注射磷酸缓冲盐溶液（PBS）组（n = 66）。所有受试者在初免注射36周后接受2012/13季节性三价灭活流感疫苗（IIV3）。疫苗安全性和耐受性是主要目标，通过血凝抑制（HAI）测量抗体反应是次要目标。
DNA疫苗初免-IIV3加强方案安全且耐受性良好。本研究未检测到DNA疫苗初免组和PBS初免组之间HAI反应的显著差异。
虽然在先前的研究中DNA初免显著改善了对传统单价H5疫苗的反应，但在使用季节性流感毒株时对成年人无效，这可能是由于对初免疫苗已有的免疫力、初免和加强抗原不匹配或36周的漫长加强间隔。在进一步评估这种疫苗策略时，可能需要仔细优化与抗原匹配、疫苗接种间隔以及对流感已有的免疫反应相关的DNA初免-IIV3加强方案。特别是，在较少接触季节性流感毒株的较年轻年龄组中测试这一概念可能会提供有用信息。
ClinicalTrials.gov NCT01498718。
