Development of T Follicular Helper Cell-independent Nanoparticle Vaccines for SARS-CoV-2 or HIV-1 by Targeting ICOSL

Overview

Journal NPJ Vaccines

Date 2024 Sep 28

PMID 39341822

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

Affiliations

Soon will be listed here.

Abstract

T helper cells, particularly T follicular helper (T) cells, are essential for the neutralizing antibody production elicited by pathogens or vaccines. However, in immunocompromised individuals, the inefficient support from T 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-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 cells to support B cell response, which is significant for the immunocompromised people, such as the elderly or HIV-1-infected individuals.

Citing Articles

ICOSLG Is Associated with Anti-PD-1 and Concomitant Antihistamine Treatment Response in Advanced Melanoma.

Mallardo D, Fordellone M, Ottaviano M, Marano G, Vitale M, Mallardo M Int J Mol Sci. 2024; 25(22).

PMID: 39596506 PMC: 11594639. DOI: 10.3390/ijms252212439.

References

Collier D, Ferreira I, Kotagiri P, Datir R, Lim E, Touizer E . Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2. Nature. 2021; 596(7872):417-422. PMC: 8373615. DOI: 10.1038/s41586-021-03739-1. View

Hu H, Wu X, Jin W, Chang M, Cheng X, Sun S . Noncanonical NF-kappaB regulates inducible costimulator (ICOS) ligand expression and T follicular helper cell development. Proc Natl Acad Sci U S A. 2011; 108(31):12827-32. PMC: 3150902. DOI: 10.1073/pnas.1105774108. View

Crotty S . T follicular helper cell differentiation, function, and roles in disease. Immunity. 2014; 41(4):529-42. PMC: 4223692. DOI: 10.1016/j.immuni.2014.10.004. View

Banga R, Procopio F, Noto A, Pollakis G, Cavassini M, Ohmiti K . PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals. Nat Med. 2016; 22(7):754-61. DOI: 10.1038/nm.4113. View

Hedl M, Lahiri A, Ning K, Cho J, Abraham C . Pattern recognition receptor signaling in human dendritic cells is enhanced by ICOS ligand and modulated by the Crohn's disease ICOSLG risk allele. Immunity. 2014; 40(5):734-46. PMC: 4157904. DOI: 10.1016/j.immuni.2014.04.011. View

Doitsh G, Greene W . Dissecting How CD4 T Cells Are Lost During HIV Infection. Cell Host Microbe. 2016; 19(3):280-91. PMC: 4835240. DOI: 10.1016/j.chom.2016.02.012. View

Pal R, Bhadada S, Misra A . COVID-19 vaccination in patients with diabetes mellitus: Current concepts, uncertainties and challenges. Diabetes Metab Syndr. 2021; 15(2):505-508. PMC: 7904463. DOI: 10.1016/j.dsx.2021.02.026. View

Liu D, Xu H, Shih C, Wan Z, Ma X, Ma W . T-B-cell entanglement and ICOSL-driven feed-forward regulation of germinal centre reaction. Nature. 2014; 517(7533):214-8. DOI: 10.1038/nature13803. View

Sette A, Sidney J, Crotty S . T Cell Responses to SARS-CoV-2. Annu Rev Immunol. 2023; 41:343-373. DOI: 10.1146/annurev-immunol-101721-061120. View

10.

Crotty S . T Follicular Helper Cell Biology: A Decade of Discovery and Diseases. Immunity. 2019; 50(5):1132-1148. PMC: 6532429. DOI: 10.1016/j.immuni.2019.04.011. View

11.

Kwak K, Akkaya M, Pierce S . B cell signaling in context. Nat Immunol. 2019; 20(8):963-969. DOI: 10.1038/s41590-019-0427-9. View

12.

Peters L, Raymer D, Pal J, Ambardekar A . Association of COVID-19 Vaccination With Risk of COVID-19 Infection, Hospitalization, and Death in Heart Transplant Recipients. JAMA Cardiol. 2022; 7(6):651-654. PMC: 9047723. DOI: 10.1001/jamacardio.2022.0670. View

13.

Nurieva R, Chung Y, Hwang D, Yang X, Kang H, Ma L . Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity. 2008; 29(1):138-49. PMC: 2556461. DOI: 10.1016/j.immuni.2008.05.009. View

14.

Chen R, Zhang X, Yuan Y, Deng X, Wu B, Xi Z . Development of Receptor Binding Domain (RBD)-Conjugated Nanoparticle Vaccines with Broad Neutralization against SARS-CoV-2 Delta and Other Variants. Adv Sci (Weinh). 2022; 9(11):e2105378. PMC: 9008796. DOI: 10.1002/advs.202105378. View

15.

Wang B, Jiang H, Zhou T, Ma N, Liu W, Wang Y . Expression of ICOSL is associated with decreased survival in invasive breast cancer. PeerJ. 2019; 7:e6903. PMC: 6526018. DOI: 10.7717/peerj.6903. View

16.

Boyarsky B, Chiang T, Ou M, Werbel W, Massie A, Segev D . Antibody Response to the Janssen COVID-19 Vaccine in Solid Organ Transplant Recipients. Transplantation. 2021; 105(8):e82-e83. PMC: 8298284. DOI: 10.1097/TP.0000000000003850. View

17.

Cubas R, Mudd J, Savoye A, Perreau M, van Grevenynghe J, Metcalf T . Inadequate T follicular cell help impairs B cell immunity during HIV infection. Nat Med. 2013; 19(4):494-9. PMC: 3843317. DOI: 10.1038/nm.3109. View

18.

Zhang X, Yuan Y, Wu B, Wang X, Lin Y, Luo Y . Improvement of a SARS-CoV-2 vaccine by enhancing the conjugation efficiency of the immunogen to self-assembled nanoparticles. Cell Mol Immunol. 2021; 18(8):2042-2044. PMC: 8287548. DOI: 10.1038/s41423-021-00736-2. View

19.

Victora G, Nussenzweig M . Germinal Centers. Annu Rev Immunol. 2022; 40:413-442. DOI: 10.1146/annurev-immunol-120419-022408. View

20.

Yu F, Li Q, Chen X, Liu J, Li L, Li B . X4-Tropic Latent HIV-1 Is Enriched in Peripheral Follicular Helper T Cells and Is Correlated with Disease Progression. J Virol. 2019; 94(2). PMC: 6955254. DOI: 10.1128/JVI.01219-19. View