{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:30:14Z","timestamp":1787016614597,"version":"build-2736575974"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2017,5,1]],"date-time":"2017-05-01T00:00:00Z","timestamp":1493596800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Li Ka-Shing Foundation in Hong Kong"},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2013ZX10004003003003"],"award-info":[{"award-number":["2013ZX10004003003003"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2012AA02A404"],"award-info":[{"award-number":["2012AA02A404"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Current seasonal influenza vaccines are efficacious when vaccine strains are matched with circulating strains. However, they do not protect antigenic variants and newly emerging pandemic and outbreak strains. Thus, there is a critical need for developing so-called \u201cuniversal\u201d vaccines that protect against all influenza viruses. In the present study, we developed a bivalent heterologous DNA virus-like particle prime-boost vaccine strategy. We show that mice immunized with this vaccine were broadly protected against lethal challenge from group 1 (H1, H5, and H9) and group 2 (H3 and H7) viruses, with 94% aggregate survival. To determine the immune correlates of protection, we performed passive immunizations and\n                    <jats:italic>in vitro<\/jats:italic>\n                    assays. We show that this vaccine elicited antibody responses that bound HA from group 1 (H1, H2, H5, H6, H8, H9, H11, and H12) and group 2 (H3, H4, H7, H10, H14, and H15) and neutralized homologous and intrasubtypic H5 and H7 and heterosubtypic H1 viruses and hemagglutinin-specific CD4 and CD8 T cell responses. As a result, passive immunization with immune sera fully protected mice against H5, H7, and H1 challenge, whereas with both immune sera and T cells the mice survived heterosubtypic H3 and H9 challenge. Thus, it appears that (i) neutralizing antibodies alone fully protect against homologous and intrasubtypic H5 and H7 and (ii) neutralizing and binding antibodies are sufficient to protect against heterosubtypic H1, (iii) but against heterosubtypic H3 and H9, binding antibodies and T cells are required for complete survival. We believe that this vaccine regimen could potentially be a candidate for a \u201cuniversal\u201d influenza vaccine.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    Influenza virus infection is global health problem. Current seasonal influenza vaccines are efficacious only when vaccine strains are matched with circulating strains. However, these vaccines do not protect antigenic variants and newly emerging pandemic and outbreak strains. Because of this, there is an urgent need to develop so-called \u201cuniversal\u201d influenza vaccines that can protect against both current and future influenza strains. In the present study, we developed a bivalent heterologous prime-boost vaccine strategy. We show that a bivalent vaccine regimen elicited broad binding and neutralizing antibody and T cell responses that conferred broad protection against diverse challenge viruses in mice, suggesting that this bivalent prime-boost strategy could practically be a candidate for a \u201cuniversal\u201d influenza vaccine.\n                  <\/jats:p>","DOI":"10.1128\/jvi.02052-16","type":"journal-article","created":{"date-parts":[[2017,2,8]],"date-time":"2017-02-08T20:50:25Z","timestamp":1486587025000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["A Bivalent Heterologous DNA Virus-Like-Particle Prime-Boost Vaccine Elicits Broad Protection against both Group 1 and 2 Influenza A Viruses"],"prefix":"10.1128","volume":"91","author":[{"given":"Wenbo","family":"Jiang","sequence":"first","affiliation":[{"name":"Unit of Antiviral Immunity and Genetic Therapy, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangshuang","family":"Wang","sequence":"additional","affiliation":[{"name":"Unit of Antiviral Immunity and Genetic Therapy, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China"},{"name":"Shanghai Tech University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglin","family":"Chen","sequence":"additional","affiliation":[{"name":"The University of Hong Kong, Hong Kong Special Administrative Region, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Ren","sequence":"additional","affiliation":[{"name":"Unit of Antiviral Immunity and Genetic Therapy, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Huang","sequence":"additional","affiliation":[{"name":"Unit of Antiviral Immunity and Genetic Therapy, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiqin","family":"Wang","sequence":"additional","affiliation":[{"name":"Unit of Antiviral Immunity and Genetic Therapy, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4717-0747","authenticated-orcid":false,"given":"Ze","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Biological Products, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Chen","sequence":"additional","affiliation":[{"name":"The University of Hong Kong, Hong Kong Special Administrative Region, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9192-9231","authenticated-orcid":false,"given":"Paul","family":"Zhou","sequence":"additional","affiliation":[{"name":"Unit of Antiviral Immunity and Genetic Therapy, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China"},{"name":"Shanghai Tech University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Influenza at the human-animal interface","author":"World Health Organization","year":"2016","unstructured":"World Health Organization. 2016. 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