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Vaccine. 2017 Jun 27;35(30):3741-3748. doi: 10.1016/j.vaccine.2017.05.053. Epub 2017 May 31.

Nontoxic outer membrane vesicles efficiently increase the efficacy of an influenza vaccine in mice and ferrets.

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Department of Pharmacy, College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Republic of Korea.
Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
Department of Pharmacy, College of Pharmacy, Chungbuk National University, 52 Naesudong-ro, Heungdeok-gu, Cheongju, Chungcheongbuk-do 28644, Republic of Korea.
College of Veterinary Medicine, Gyeongsang National University, 501 Jinjudae-ro, Jinju, Gyeongsangnam-do 52828, Republic of Korea. Electronic address:
Department of Pharmacy, College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Republic of Korea. Electronic address:


In this study, we developed a further-modified outer membrane vesicle (fmOMV) from the ΔmsbB/ΔpagP mutant of Escherichia coli transformed with the plasmid, pLpxF, in order to use it as an adjuvant for pandemic H1N1 (pH1N1) influenza vaccine. We evaluated the efficacy of the pH1N1 influenza vaccine containing the fmOMV in animal models as compared to the commercial adjuvants, alum or AddaVaxTM. The fmOMV-adjuvanted pH1N1 influenza vaccine induced a significant increase in the humoral immunity; however, this effect was less than that of the AddaVaxTM. The fmOMV-adjuvanted vaccine displayed pronounced an enhanced protective efficacy with increased T cell immune response and reduced the viral load in the lungs of the infected mice after challenging them with a lethal dose of the homologous virus. Moreover, it resulted in a significantly higher cross-protection against heterologous virus challenge than that of the pH1N1 vaccine with alum or with no adjuvants. In ferrets, the fmOMV-adjuvanted vaccine elicited a superior antibody response based on the HI titer and efficiently protected the animals from the lethal viral challenges. Taken together, the nontoxic fmOMV could be a promising adjuvant for inducing robust T cell priming into the pH1N1 vaccine and might be broadly applicable to the development of preventive measures against influenza virus infection.


Adjuvant; Influenza; Pandemic; T cell; fmOMV

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