Development of T follicular helper cell-independent nanoparticle vaccines for SARS-CoV-2 or HIV-1 by targeting ICOSL

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Abstract

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

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T Follicular Helper Cell Biology: A Decade of Discovery and Diseases

Shane Crotty (2019)

Helping B cells and antibody responses is a major function of CD4+ T cells. It has been 10 years since the publication of Bcl6 as the lineage-defining transcription factor for T follicular helper (Tfh) differentiation and the requirement of Tfh cells as the specialized subset of CD4+ T cells needed for germinal centers (the microanatomical sites of B cell mutation and antibody affinity maturation) and related B cell responses. A great deal has been learned about Tfh cells in the past 10 years, particularly regarding their roles in a surprising range of diseases. Advances in the understanding of Tfh cell differentiation and function are discussed, as are the understanding of Tfh cells in infectious diseases, vaccines, autoimmune diseases, allergies, atherosclerosis, organ transplants, and cancer. This includes discussion of Tfh cells in the human immune system. Based on the discoveries to date, the next decade of Tfh research surely holds many more surprises. VIDEO ABSTRACT.

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Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine

Paul Heath, Eva Galiza, David Baxter … (2021)

Background Early clinical data from studies of the NVX-CoV2373 vaccine (Novavax), a recombinant nanoparticle vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that contains the full-length spike glycoprotein of the prototype strain plus Matrix-M adjuvant, showed that the vaccine was safe and associated with a robust immune response in healthy adult participants. Additional data were needed regarding the efficacy, immunogenicity, and safety of this vaccine in a larger population. Methods In this phase 3, randomized, observer-blinded, placebo-controlled trial conducted at 33 sites in the United Kingdom, we assigned adults between the ages of 18 and 84 years in a 1:1 ratio to receive two intramuscular 5-μg doses of NVX-CoV2373 or placebo administered 21 days apart. The primary efficacy end point was virologically confirmed mild, moderate, or severe SARS-CoV-2 infection with an onset at least 7 days after the second injection in participants who were serologically negative at baseline. Results A total of 15,187 participants underwent randomization, and 14,039 were included in the per-protocol efficacy population. Of the participants, 27.9% were 65 years of age or older, and 44.6% had coexisting illnesses. Infections were reported in 10 participants in the vaccine group and in 96 in the placebo group, with a symptom onset of at least 7 days after the second injection, for a vaccine efficacy of 89.7% (95% confidence interval [CI], 80.2 to 94.6). No hospitalizations or deaths were reported among the 10 cases in the vaccine group. Five cases of severe infection were reported, all of which were in the placebo group. A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups. Conclusions A two-dose regimen of the NVX-CoV2373 vaccine administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant. (Funded by Novavax; EudraCT number, 2020-004123-16 .)

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T follicular helper cell differentiation, function, and roles in disease.

Shane Crotty (2014)

Follicular helper T (Tfh) cells are specialized providers of T cell help to B cells, and are essential for germinal center formation, affinity maturation, and the development of most high-affinity antibodies and memory B cells. Tfh cell differentiation is a multistage, multifactorial process involving B cell lymphoma 6 (Bcl6) and other transcription factors. This article reviews understanding of Tfh cell biology, including their differentiation, migration, transcriptional regulation, and B cell help functions. Tfh cells are critical components of many protective immune responses against pathogens. As such, there is strong interest in harnessing Tfh cells to improve vaccination strategies. Tfh cells also have roles in a range of other diseases, particularly autoimmune diseases. Overall, there have been dramatic advances in this young field, but there is much to be learned about Tfh cell biology in the interest of applying that knowledge to biomedical needs.

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Author and article information

Contributors

Xin He:

ORCID: http://orcid.org/0000-0002-2131-2092

hexin59@mail.sysu.edu.cn

Journal

Journal ID (nlm-ta): NPJ Vaccines

Journal ID (iso-abbrev): NPJ Vaccines

Title: NPJ Vaccines

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2059-0105

Publication date (Electronic): 28 September 2024

Publication date PMC-release: 28 September 2024

Publication date Collection: 2024

Volume: 9

Electronic Location Identifier: 176

Affiliations

[1 ]Institute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, ( https://ror.org/0064kty71) Guangzhou, China

[2 ]Guangzhou Laboratory, Bio-island, Guangzhou, China

[3 ]GRID grid.470124.4, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, , the First Affiliated Hospital of Guangzhou Medical University, ; Guangzhou, China

[4 ]GRID grid.413405.7, ISNI 0000 0004 1808 0686, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, , Guangzhou, ; Guangdong, China

[5 ]Shenzhen College of International Education, No. 3 Antuoshan 6th Road, Futian District, Shenzhen, China

[6 ]Center for Infection and Immunity Study, School of Medicine, Sun Yat-sen University, ( https://ror.org/0064kty71) Shenzhen, China

Author information

Xin He http://orcid.org/0000-0002-2131-2092

Article

Publisher ID: 971

DOI: 10.1038/s41541-024-00971-4

PMC ID: 11438966

PubMed ID: 39341822

SO-VID: 59b7b14d-c50c-4519-80d4-46a83c1fa6b6

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Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

History

Date received : 25 February 2024

Date accepted : 19 September 2024

Funding

Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);

Award ID: 32100743

Award Recipient : Xin He

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Keywords: protein vaccines,preclinical research

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Keywords: protein vaccines, preclinical research

Development of T follicular helper cell-independent nanoparticle vaccines for SARS-CoV-2 or HIV-1 by targeting ICOSL

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Novel Coronavirus Disease COVID-19

Most cited references 57

T Follicular Helper Cell Biology: A Decade of Discovery and Diseases

Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine

T follicular helper cell differentiation, function, and roles in disease.

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