Needle-free delivery of DNA: Targeting of hemagglutinin to MHC class II molecules protects rhesus macaques against H1N1 influenza

被引:15
|
作者
Mooij, Petra [1 ]
Grodeland, Gunnveig [2 ,3 ]
Koopman, Gerrit [1 ]
Andersen, Tor Kristian [2 ,3 ]
Mortier, Daniella [1 ]
Nieuwenhuis, Ivonne G. [1 ]
Verschoor, Ernst J. [1 ]
Fagrouch, Zahra [1 ]
Bogers, Willy M. [1 ]
Bogen, Bjarne [2 ,3 ]
机构
[1] Biomed Primate Res Ctr, Rijswijk, Netherlands
[2] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Influenza Vaccine Res, N-0027 Oslo, Norway
[3] Oslo Univ Hosp, N-0027 Oslo, Norway
基金
欧盟第七框架计划;
关键词
Influenza; DNA vaccine; Antigen presenting cell; APC-targeted antigen; Non-human primates; ANTIGEN-PRESENTING CELLS; NONHUMAN-PRIMATES; IN-VIVO; VACCINE; RESPONSES; IMMUNOGENICITY; LYMPHOCYTES; EFFICACY; INSIGHTS;
D O I
10.1016/j.vaccine.2018.12.049
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Conventional influenza vaccines are hampered by slow and limited production capabilities, whereas DNA vaccines can be rapidly produced for global coverage in the event of an emerging pandemic. However, a drawback of DNA vaccines is their generally low immunogenicity in non-human primates and humans. We have previously demonstrated that targeting of influenza hemagglutinin to human HLA class II molecules can increase antibody responses in larger animals such as ferrets and pigs. Here, we extend these observations by immunizing non-human primates (rhesus macaques) with a DNA vaccine encoding a bivalent fusion protein that targets influenza virus hemagglutinin (HA) to Mamu class II molecules. Such immunization induced neutralizing antibodies and antigen-specific T cells. The DNA was delivered by pain- and needle-free jet injections intradermally. No adverse effects were observed. Most importantly, the immunized rhesus macaques were protected against a challenge with influenza virus. (C) 2019 The Authors. Published by Elsevier Ltd.
引用
收藏
页码:817 / 826
页数:10
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