{"title":"Development of T follicular helper cell-independent nanoparticle vaccines for SARS-CoV-2 or HIV-1 by targeting ICOSL.","authors":"Yongli Zhang, Achun Chen, Daiying Li, Quyu Yuan, Airu Zhu, Jieyi Deng, Yalin Wang, Jie Liu, Chaofeng Liang, Wenjie Li, Qiannan Fang, Jiatong Xie, Xiantao Zhang, Xu Zhang, Yiwen Zhang, Ran Chen, Ting Pan, Hui Zhang, Xin He","doi":"10.1038/s41541-024-00971-4","DOIUrl":null,"url":null,"abstract":"<p><p>T helper cells, particularly T follicular helper (T<sub>FH</sub>) cells, are essential for the neutralizing antibody production elicited by pathogens or vaccines. However, in immunocompromised individuals, the inefficient support from T<sub>FH</sub> cells could lead to limited protection after vaccine inoculation. Here we showed that the conjugation of inducible T cell costimulatory (ICOS) onto the nanoparticle, together with immunogen, significantly enhanced the immune response of the vaccines specific for SARS-CoV-2 or human immunodeficiency virus type-1 (HIV-1) in T<sub>FH</sub>-deficient mice. Further studies indicated that ICOSL on B cells was triggered by ICOS binding, subsequently activated the PKCβ signaling pathway, and enhanced the survival and proliferation of B cells. Our findings revealed that the stimulation of ICOS-ICOSL interaction by adding ICOS on the nanoparticle vaccine significantly substitutes the function of T<sub>FH</sub> cells to support B cell response, which is significant for the immunocompromised people, such as the elderly or HIV-1-infected individuals.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"176"},"PeriodicalIF":6.9000,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438966/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NPJ Vaccines","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41541-024-00971-4","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
T helper cells, particularly T follicular helper (TFH) cells, are essential for the neutralizing antibody production elicited by pathogens or vaccines. However, in immunocompromised individuals, the inefficient support from TFH cells could lead to limited protection after vaccine inoculation. Here we showed that the conjugation of inducible T cell costimulatory (ICOS) onto the nanoparticle, together with immunogen, significantly enhanced the immune response of the vaccines specific for SARS-CoV-2 or human immunodeficiency virus type-1 (HIV-1) in TFH-deficient mice. Further studies indicated that ICOSL on B cells was triggered by ICOS binding, subsequently activated the PKCβ signaling pathway, and enhanced the survival and proliferation of B cells. Our findings revealed that the stimulation of ICOS-ICOSL interaction by adding ICOS on the nanoparticle vaccine significantly substitutes the function of TFH cells to support B cell response, which is significant for the immunocompromised people, such as the elderly or HIV-1-infected individuals.
NPJ VaccinesImmunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍:
Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.