Neutrophils recruited to immunization sites initiating vaccine-induced antibody responses by locally expressing BAFF

Wang, Yangyang; Qu, Kuo; Lu, Weiyue; Zhao, Peiyan; Wang, Zhe; Cui, Cuiyun; Liu, Ye; Yang, Ming; Yu, Yongli; Wang, Liying

doi:10.1016/j.isci.2022.104453

Cited by 4 publications

(2 citation statements)

References 42 publications

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“…B-cell activating and survival factors, like B-cell activating factor (BAFF), A-proliferation inducing ligand (APRIL) and CD40L ligand (CD40L), are mainly implicated in B-cell survival, proliferation and antibody production and T-cell dependent and independent antibody class switching ( 25 – 27 ). After vaccination their concentrations increases enhancing B-cell activation ( 28 , 29 ), and their expression is a prerequisite for activation of adaptive immune response to vaccination, while their absence may result in a reduced magnitude of response ( 27 ). Being involved in B-cell differentiation and survival, the three cytokines are target for immune modulation in the context of vaccine design and have been recently studied as molecular adjuvants to improve vaccine outcome ( 30 ).…”

Section: Introductionmentioning

confidence: 99%

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

et al. 2022

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BackgroundThe mRNA vaccines help protect from COVID-19 severity, however multiple sclerosis (MS) disease modifying therapies (DMTs) might affect the development of humoral and T-cell specific response to vaccination.MethodsThe aim of the study was to evaluate humoral and specific T-cell response, as well as B-cell activation and survival factors, in people with MS (pwMS) under DMTs before (T0) and after two months (T1) from the third dose of vaccine, comparing the obtained findings to healthy donors (HD). All possible combinations of intracellular IFNγ, IL2 and TNFα T-cell production were evaluated, and T-cells were labelled “responding T-cells”, those cells that produced at least one of the three cytokines of interest, and “triple positive T-cells”, those cells that produced simultaneously all the three cytokines.ResultsThe cross-sectional evaluation showed no significant differences in anti-S antibody titers between pwMS and HD at both time-points. In pwMS, lower percentages of responding T-cells at T0 (CD4: p=0.0165; CD8: p=0.0022) and triple positive T-cells at both time-points compared to HD were observed (at T0, CD4: p=0.0007 and CD8: p=0.0703; at T1, CD4: p=0.0422 and CD8: p=0.0535). At T0, pwMS showed higher plasma levels of APRIL, BAFF and CD40L compared to HD (p<0.0001, p<0.0001 and p<0.0001, respectively) and at T1, plasma levels of BAFF were still higher in pwMS compared to HD (p=0.0022).According to DMTs, at both T0 and T1, lower anti-S antibody titers in the depleting/sequestering-out compared to the enriching-in pwMS subgroup were found (p=0.0410 and p=0.0047, respectively) as well as lower percentages of responding CD4+ T-cells (CD4: p=0.0394 and p=0.0004, respectively). Moreover, the depleting/sequestering-out subgroup showed higher percentages of IFNγ-IL2-TNFα+ T-cells at both time-points, compared to the enriching-in subgroup in which a more heterogeneous cytokine profile was observed (at T0 CD4: p=0.0187; at T0 and T1 CD8: p =0.0007 and p =0.0077, respectively).ConclusionIn pwMS, humoral and T-cell response to vaccination seems to be influenced by the different DMTs. pwMS under depleting/sequestering-out treatment can mount cellular responses even in the presence of a low positive humoral response, although the cellular response seems qualitatively inferior compared to HD. An understanding of T-cell quality dynamic is needed to determine the best vaccination strategy and in general the capability of immune response in pwMS under different DMT.

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Section: Introductionmentioning

confidence: 99%

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

et al. 2022

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“…CD4+ T cells were important both in humoral and cellular immune responses. The neutrophils played an important role in the innate immune responses, and it has been reported that they are required during vaccination for host protection and for promoting the antibody responses at immunization sites [ 11 ]. These results indicated that the Hib vaccines could induce a high level of antibodies.…”

Section: Resultsmentioning

confidence: 99%

Systematic Evaluation of the Distribution of Immune Cells following Subcutaneous Administration of Haemophilus Influenzae Type B Vaccine to Mice

He,

Zhao,

Liang

et al. 2023

Diseases

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The Haemophilus influenzae type B (Hib) conjugate vaccine is the most effective way to prevent Hib infection in infants and young children, and it is designed to induce the production of antibodies against polyribosylribitol phosphate (PRP) to protect babies from infection. However, the mechanism of immunity induced by the Hib vaccine is not fully understood. Recently, with the development of the combination diphtheria and tetanus toxoids and acellular pertussis vaccines (DTaP), increasing numbers of manufacturers have begun to develop DTaP-based combination vaccines, like the combination vaccine diphtheria and tetanus toxoids and acellular pertussis and Hib conjugate vaccine (DTaP-Hib), which contains adjuvants. However, the Hib vaccine does not contain adjuvants. It was theorized that the Hib antigen has poor compatibility with aluminum adjuvants for unclear reasons. Therefore, understanding the mechanism of the Hib-vaccine-induced immune response and the influence of adjuvants on the Hib vaccine is of great significance. In this paper, we immunized BalBc mice with either the Hib vaccine or the Hib vaccine that adsorbs aluminum adjuvants (Hib-Al). Here, we analyzed the anti-PRP antibody level and immune response of different cells using cell and cytokine levels. We found that the Hib vaccine could induce a humoral and cellular immune response, and the Hib-Al vaccine could induce greater quantities of IFN-γ, IL-4, and IL-6 and more antigen-specific antibodies through B cells, Th1, Th2, and ILC3s in the spleen. Together, our findings demonstrate the serologic responses and immune response in terms of cell and cytokine levels induced by the Hib vaccine, and they also imply that the addition of aluminum hydroxide adjuvant could enhance the function of the Hib vaccine, which preliminarily reveals the mechanism of immune response induced by the Hib-related vaccine.

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Trailblazing in adjuvant research: succinate’s uncharted territory with neutrophils

Wang,

Xiu,

et al. 2024

American Journal of Physiology-Cell Physiology

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The purpose of this study is to investigate the previously unknown connection that succinate has with neutrophils in the setting of adjuvant-mediated immunological enhancement. It has been discovered that succinates stimulate the recruitment of neutrophils in immunization sites, which in turn induces the expression of what is known as neutrophil-derived B cell-activating factor (BAFF). Further amplification of vaccine-induced antibody responses is provided via the SUCNR1-IRF5-BAFF signaling pathway, which provides insights into a unique mechanism for immunological enhancement.

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Neutrophils recruited to immunization sites initiating vaccine-induced antibody responses by locally expressing BAFF

Cited by 4 publications

References 42 publications

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

Systematic Evaluation of the Distribution of Immune Cells following Subcutaneous Administration of Haemophilus Influenzae Type B Vaccine to Mice

Trailblazing in adjuvant research: succinate’s uncharted territory with neutrophils

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