Dataset Information

CD154 Expression Indicates T Cell Activation Following Tetanus Toxoid Vaccination of Horses.

ABSTRACT: Despite the relevance of adaptive immunity against equine pathogens antigen-specific T cell responses of horses are not well characterized and the lack of insight into T cell responses hampers the understanding of the pathogeneses of important diseases. In this study we used tetanus toxoid (TT) as a well-defined antigen to characterize antigen-reactive T cells. Six healthy adult horses received a routine booster against tetanus with an immune stimulating complex (ISCOM)-based vaccine and were followed for 28 days. TT-specific serum antibodies were quantified by ELISA and increased in all horses by day 7 after vaccination. CD154 is an established indicator of antigen-reactive T helper cells in other species, but has not been characterized in horses. CD154 detection in equine PBMC by an anti-human CD154 antibody (clone 5C8) was confirmed by Western blots and then applied for flow cytometry. As a common indicator of equine T cell activation, cytokine induction was studied in parallel. T cells were analyzed by multicolor flow cytometry of PBMC after re-stimulation with TT in vitro. Reactive T helper (Th) cells were characterized by increased frequencies of CD4⁺CD154⁺ lymphocytes in in vitro TT-re-stimulated PBMC on day 14 after vaccination of the horses compared to pre-vaccination. The majority of all CD154⁺ cells after TT re-stimulation were CD4⁺ Th cells, but CD154 was also induced on CD4^- cells albeit in lower frequencies. CD154⁺CD4⁺ Th cells were enriched in cytokine-expressing cells compared to CD154^-CD4⁺ Th cells. Similar to the CD4⁺CD154⁺ frequencies, CD4⁺IL-4⁺, CD4⁺IFN-γ⁺ and CD4⁺TNF-α⁺ were increased after vaccination, but IL-4⁺ increased later than IFN-γ⁺ and CD4⁺TNF-α⁺, which already exceeded pre-vaccination frequencies on day 7. CD4⁺CD154⁺ frequencies correlated positively with those of CD4⁺IL-4⁺ (Th2) on day 14, and negatively with CD4⁺IFN-γ⁺ induction on day 7, but did not correlate with CD4⁺TNF-α⁺ frequencies or TT-specific antibody concentrations. CD154 appears to be a useful marker of antigen-reactive equine Th cells in combination with cytokine expression. The T cell analyses established here with TT can be applied to other antigens relevant for infections or allergies of horses and in horse models for translational research.

SUBMITTER: Schnabel CL

PROVIDER: S-EPMC9043809 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CD154 Expression Indicates T Cell Activation Following Tetanus Toxoid Vaccination of Horses.

Schnabel Christiane L CL Fletemeyer Babette B Lübke Sabrina S Marti Eliane E Wagner Bettina B Alber Gottfried G

Frontiers in immunology 20220413

Despite the relevance of adaptive immunity against equine pathogens antigen-specific T cell responses of horses are not well characterized and the lack of insight into T cell responses hampers the understanding of the pathogeneses of important diseases. In this study we used tetanus toxoid (TT) as a well-defined antigen to characterize antigen-reactive T cells. Six healthy adult horses received a routine booster against tetanus with an immune stimulating complex (ISCOM)-based vaccine and were fo ...[more]

PMID: 35493462

Similar Datasets

Project description:Cervical cancer is the fourth most common cancer in women with an estimated 570,000 new cases in 2018 which constitute about 6. 6% of all cancers in women according to WHO report 2018. Approximately 90% of the 270,000 deaths from cervical cancer in 2015 occurred in low- and middle-income countries. In cervical cancers, which is caused by human papillomavirus (HPV) infection, the expression of HPV 16 E6 and E7 proteins are essential for tumor cell transformation and maintenance of malignancy. Prophylactic vaccines against cervical cancer caused by human papillomavirus have not proven successful. Although virus-like particle-based (VLPs) vaccines have been developed with prophylactic activities to prevent most HPV infections, the therapeutic effect of VLP vaccines has yet to be demonstrated for those who were already infected. A recent study showed that pre-conditioning mice with a potent antigen such as tetanus toxoid significantly improves lymph node homing and efficacy of dendritic cells. Tetanus toxoid has also been used in combination with DNA vaccines designed from tumor based antigens. In the present study, we pre-conditioned mice with tetanus toxoid followed by vaccination with a Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) overexpressing tumor-cell based vaccine (GVAX). We observed that pre-conditioning with tetanus toxoid followed by vaccination with GVAX regressed tumor growth and enhanced the overall survival of the mice. Pre-conditioning with tetanus toxoid enhanced the immune response which was observed by enlarged spleen size, higher proliferation rate of lymphocytes, a higher level of IFN-γ, TNF-α, and IL-4 antigen-specific secretions by the splenocytes. Pre-conditioning with tetanus toxoid increased memory T cell migration into the tumor site and spleen. The antigen-specific cytotoxic T cell lysis percentage was also found to be higher in the group of mice vaccinated with the combination of tetanus toxoid and GVAX. Hence, pre-conditioning with tetanus toxoid prior to vaccination with a tumor-cell based vaccine overexpressing GM-CSF might be an effective strategy for targeting E7-specific HPV-associated cervical malignancy.

Project description:BackgroundThe immunogenicity and safety of a booster dose of tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT), alone or co-administered with MenB vaccine, were assessed in healthy 13-25-year olds who received MenACYW-TT or a CRM-conjugate vaccine (MCV4-CRM) 3-6 years earlier.MethodsThis phase IIIb open-label trial (NCT04084769) evaluated MenACYW-TT-primed participants, randomized to receive MenACYW-TT alone or with a MenB vaccine, and MCV4-CRM-primed participants who received MenACYW-TT alone. Functional antibodies against serogroups A, C, W and Y were measured using human complement serum bactericidal antibody assay (hSBA). The primary endpoint was vaccine seroresponse (post-vaccination titers ≥1:16 if pre-vaccination titers <1:8; or a ≥4-fold increase if pre-vaccination titers ≥1:8) 30 days post booster. Safety was evaluated throughout the study.ResultsThe persistence of the immune response following primary vaccination with MenACYW-TT was demonstrated. Seroresponse after MenACYW-TT booster was high regardless of priming vaccine (serogroup A: 94.8% vs 93.2%; C: 97.1% vs 98.9%; W: 97.7% vs 98.9%; and Y; 98.9% vs 100% for MenACWY-TT-primed and MCV4-CRM-primed groups, respectively). Co-administration with MenB vaccines did not affect MenACWY-TT immunogenicity. No vaccine-related serious adverse events were reported.ConclusionsMenACYW-TT booster induced robust immunogenicity against all serogroups, regardless of the primary vaccine received, and had an acceptable safety profile.ImpactA booster dose of MenACYW-TT induces robust immune responses in children and adolescents primed with MenACYW-TT or another MCV4 (MCV4-DT or MCV4-CRM), respectively. Here, we demonstrate that MenACYW-TT booster 3-6 years after primary vaccination induced robust immunogenicity against all serogroups, regardless of the priming vaccine (MenACWY-TT or MCV4-CRM), and was well tolerated. Persistence of the immune response following previous primary vaccination with MenACYW-TT was demonstrated. MenACYW-TT booster with MenB vaccine co-administration did not affect MenACWY-TT immunogenicity and was well tolerated. These findings will facilitate the provision of broader protection against IMD particularly in higher-risk groups such as adolescents.

Project description:BackgroundTetanus is a bacterial disease caused by the Clostridium tetani, which is a highly fatal, noncommunicable, and toxin-mediated disease. Globally, maternal and neonatal tetanus is a public health problem due to low maternal tetanus toxoid immunization. Ethiopia has the highest neonatal mortality and morbidity related to tetanus due to low tetanus toxoid immunization and the high number of home deliveries. The main objective of this systematic review and meta-analysis was to estimate the pooled coverage of at least two doses of tetanus toxoid immunization, and the pooled effect sizes of associated factors in Ethiopia.MethodsPrimary studies for this review were searched from the PubMed/MEDLINE online, ScienceDirect, Hinari, Google, and Google Scholar databases. Primary articles published from 2010 up to August 30, 2020, were included in this meta-analysis. Data were extracted in Microsoft Excel format and exported to STATA Version 14.0. A random-effects meta-analysis model was used to estimate the pooled coverage of two or more tetanus toxoid immunizations and its associated factors. Heterogeneity was evaluated by the I 2 test. Egger's weighted regression test was used to assess publication bias.ResultsWe retrieved 212 records; of these, 199 articles were excluded for reasons. Finally, 14 studies were included in this meta-analysis. The pooled estimate of receiving at least two doses of tetanus toxoid immunization coverage in Ethiopia was 52.2% (95% CI: 42.47-61.93, I 2 = 98.4%). Antenatal care (OR = 7.8 (95% CI: 3.2, 19.2), I 2 = 96.3%), media exposure (OR = 8.3 (95% CI: 2.1, 33.3), I 2 = 98.1%), distance from the health facility (OR = 2.64 (95% CI: 1.1, 6.6), I 2 = 94.1%), educational status of women (OR = 4.7 (95% CI: 2.07, 9.56), I 2 = 94.2%), and educational status of husbands (OR = 2.995 (95% CI: 1.194, 7.512), I 2 = 92.5%) were factors significantly associated with receiving at least two doses of tetanus toxoid immunization coverage in Ethiopia.ConclusionsThe coverage of tetanus toxoid immunization among childbearing women was low in Ethiopia. Strengthening maternal health service utilization (antinatal care and institutional delivery) to the nearest health facility even in health posts and empowering education for both women and their husbands is recommended to increase tetanus toxoid immunization coverage in Ethiopia.

Dataset Information

CD154 Expression Indicates T Cell Activation Following Tetanus Toxoid Vaccination of Horses.

Publications

CD154 Expression Indicates T Cell Activation Following Tetanus Toxoid Vaccination of Horses.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets