title: Eliciting neutralizing antibodies against the membrane proximal external region of HIV-1 Env by chimeric live attenuated influenza A virus vaccines.
abstract: Despite significant efforts directed toward research on HIV-1 vaccines, a truly effective immunogen has not been achieved. However, the broadly neutralizing antibodies (BnAbs) 2F5 and 4E10, targeting the highly conserved membrane proximal external region (MPER) of HIV-1, are two promising tools for vaccine development. Here we engrafted the MPER into the linker domain between the trimeric core structure and the transmembrane domain of influenza A virus HA2 to investigate the potential of such chimeric viruses to elicit HIV-1 neutralizing antibodies. In the context of proliferating attenuated influenza A viruses, these HIV-1 neutralizing antibody epitopes could be continuously expressed and mimicked their native conformation to induce humoral immune responses. While MPER-specific antibodies could be detected in serum of guinea pigs vaccinated with the chimeric viruses, they exhibited only weakly neutralizing activities. These antisera from vaccinated animals neutralized viruses of clades B and BC (tier 1), but not of clades AE (tier 1) and C (tier 2). These results suggest that influenza A virus can be used as a vehicle for displaying MPER and inducing BnAbs, but it provides limited protection against HIV-1 infection. In the future development of HIV-1 vaccines by rational design, a more effective live virus vector or multiple antigens should be chosen to facilitate the process of neutralizing antibody maturation.
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China.
authors.forename: Dongchuan
authors.initials: D
authors.lastname: Du
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China.
authors.forename: Weiheng
authors.initials: W
authors.lastname: Su
authors.affiliation: Changchun BCHT Biotechnology Company, Changchun, China.
authors.forename: Xintao
authors.initials: X
authors.lastname: Liu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing 100050 China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Nie
authors.affiliation: Department of Cell Biology, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing 100050 China.
authors.forename: Youchun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology & Engineering, Ministry of Education, Jilin University, Changchun 130012, China. Electronic address: weikong@jlu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology & Engineering, Ministry of Education, Jilin University, Changchun 130012, China. Electronic address: jiangcl@jlu.edu.cn.
authors.forename: Chunlai
authors.initials: C
authors.lastname: Jiang
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D003429:Cross Reactions; D005260:Female; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000097:blood*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics*; D009500:Neutralization Tests; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus
keywords: Attenuated influenza A virus; HA; HIV-1 vaccine; MPER