Despite extensive research efforts, a preventive human immunodeficiency virus (HIV) vaccine remains one of the major challenges in the field of AIDS research. Experimental strategies which have been proven successful ...Despite extensive research efforts, a preventive human immunodeficiency virus (HIV) vaccine remains one of the major challenges in the field of AIDS research. Experimental strategies which have been proven successful for other viral vaccines are not enough to tackle HIV-1 and new approaches to design effective preventive AIDS vaccines are of utmost importance. Due to enormous diversity among global circulating HIV strains, an effective HIV vaccine must elicit broadly protective antibodies based responses;therefore discovering new broadly neutralizing antibodies (bNAbs) against HIV has become major focus in HIV vaccine research. However further understanding of the viral targets of such antibodies and mechanisms of action of bNAbs is required for advancement of HIV vaccine research. This technical note discusses our current knowledge on the bNAbs and immunoprophylaxis using viral vectors with their relevance in designing of new candidates to HIV-1 vaccines.展开更多
Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine development.In this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immun...Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine development.In this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immunization scheme as a solution to this task.This exploration stemmed from the rationale that gp145,a membrane-bound truncation form of HIV Env,may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode.We first showed that gp140 DNA prime-gp145 Tiantan vaccinia(TV)boost likely represents a general format for inducing potent nAb response in mice.However,when examined in rhesus macaque,this modality showed little effectiveness.To improve the efficacy,we extended the original modality by adding a strong protein boost,namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle(NP),which was generated by a newly developed click approach.The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule.Importantly,the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge.Collectively,our studies highlighted that diversification of Env immunogens,in both types and formulations,under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development.展开更多
利用Derwent Innovation平台,以(broadly neutralizing antibod*or broadly-neutralizing antibod*or bNAb*) and (HIV or human immunodeficiency virus or AIDS or acquired immune deficiency syndrome) and vaccin*为检索词,检索条...利用Derwent Innovation平台,以(broadly neutralizing antibod*or broadly-neutralizing antibod*or bNAb*) and (HIV or human immunodeficiency virus or AIDS or acquired immune deficiency syndrome) and vaccin*为检索词,检索条件是在标题或摘要中出现检索词,检索时间截至2018年8月7日,筛选出309件广谱中和抗体的专利申请,同族专利45件。该领域自1993年出现专利申请,2011年达到峰值后呈下降趋势。该领域最重要的目标市场是美国和欧洲。美国的国际艾滋病疫苗行动组织、Scripps研究所、美国国家健康研究院、杜克大学、加州大学Santa Cruz分校、儿童医学中心和纽约大学是领先的研究机构,前3位的发明人分别为杜克大学的Haynes Barton F、国际疫苗行动组织的Phogat Sanjay K和Hoffenberg Simon。该领域已具有一定的技术基础并处于改进中且与治疗有联系。展开更多
文摘Despite extensive research efforts, a preventive human immunodeficiency virus (HIV) vaccine remains one of the major challenges in the field of AIDS research. Experimental strategies which have been proven successful for other viral vaccines are not enough to tackle HIV-1 and new approaches to design effective preventive AIDS vaccines are of utmost importance. Due to enormous diversity among global circulating HIV strains, an effective HIV vaccine must elicit broadly protective antibodies based responses;therefore discovering new broadly neutralizing antibodies (bNAbs) against HIV has become major focus in HIV vaccine research. However further understanding of the viral targets of such antibodies and mechanisms of action of bNAbs is required for advancement of HIV vaccine research. This technical note discusses our current knowledge on the bNAbs and immunoprophylaxis using viral vectors with their relevance in designing of new candidates to HIV-1 vaccines.
基金This work was supported by the National Natural Science Foundation of China(81672018,81561128008)the National Basic Research Program of China(973program#2014CB542502)+2 种基金the National 13th Five-Year Grand Program on Key Infectious Disease Control(2017ZX10202102)Shanghai Pujiang Program(19PJ1409100)Intramural Funding from Shanghai Public Health Clinical Center.
文摘Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine development.In this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immunization scheme as a solution to this task.This exploration stemmed from the rationale that gp145,a membrane-bound truncation form of HIV Env,may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode.We first showed that gp140 DNA prime-gp145 Tiantan vaccinia(TV)boost likely represents a general format for inducing potent nAb response in mice.However,when examined in rhesus macaque,this modality showed little effectiveness.To improve the efficacy,we extended the original modality by adding a strong protein boost,namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle(NP),which was generated by a newly developed click approach.The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule.Importantly,the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge.Collectively,our studies highlighted that diversification of Env immunogens,in both types and formulations,under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development.
文摘利用Derwent Innovation平台,以(broadly neutralizing antibod*or broadly-neutralizing antibod*or bNAb*) and (HIV or human immunodeficiency virus or AIDS or acquired immune deficiency syndrome) and vaccin*为检索词,检索条件是在标题或摘要中出现检索词,检索时间截至2018年8月7日,筛选出309件广谱中和抗体的专利申请,同族专利45件。该领域自1993年出现专利申请,2011年达到峰值后呈下降趋势。该领域最重要的目标市场是美国和欧洲。美国的国际艾滋病疫苗行动组织、Scripps研究所、美国国家健康研究院、杜克大学、加州大学Santa Cruz分校、儿童医学中心和纽约大学是领先的研究机构,前3位的发明人分别为杜克大学的Haynes Barton F、国际疫苗行动组织的Phogat Sanjay K和Hoffenberg Simon。该领域已具有一定的技术基础并处于改进中且与治疗有联系。
