Development of T follicular helper cell-independent nanoparticle vaccines for SARS-CoV-2 or HIV-1 by targeting ICOSL
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.
Authors
- Jiatong Xie
- Ran Chen (ORCID: https://orcid.org/0009-0003-0668-9136)
- Achun Chen
- Xin He (ORCID: https://orcid.org/0000-0002-2131-2092)
- Daiying Li
- Xiantao Zhang (ORCID: https://orcid.org/0000-0002-3795-3556)
- Airu Zhu (ORCID: https://orcid.org/0000-0002-6374-4467)
- Ting Pan (ORCID: https://orcid.org/0000-0002-7106-7312)
- Yongli Zhang (ORCID: https://orcid.org/0000-0003-1700-1352)
- Wenjie Li (ORCID: https://orcid.org/0000-0003-3811-4970)
- Yiwen Zhang (ORCID: https://orcid.org/0000-0002-5232-0335)
- Xu Zhang (ORCID: https://orcid.org/0000-0002-6908-6768)
- Jie Liu (ORCID: https://orcid.org/0000-0001-6035-0131)
- Yalin Wang (ORCID: https://orcid.org/0000-0002-6241-735X)
- Qiannan Fang
- Quyu Yuan
- Chaofeng Liang
- Jieyi Deng
- Hui Zhang (ORCID: https://orcid.org/0000-0001-6300-9334)
Institutions
- Sun Yat-sen University (CN)
- Shenzhen International Travel Health Care Center (CN)
- First Affiliated Hospital of Guangzhou Medical University (CN)
- Guangzhou Regenerative Medicine and Health Guangdong Laboratory (CN)
- Guangdong Academy of Medical Sciences (CN)
- Guangdong Provincial People's Hospital (CN)
- State Key Laboratory of Respiratory Disease (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- npj Vaccines
- Published
- 2024-09-28
- DOI
- https://doi.org/10.1038/s41541-024-00971-4
- Citations
- 2
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.78
Funders
- National Natural Science Foundation of China
- Sun Yat-sen University
- Fundamental Research Funds for the Central Universities
- Basic and Applied Basic Research Foundation of Guangdong Province