Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 40082479

A functional enzymatic assay as potential readout for a clinical trial of a schistosomiasis vaccine.

Desalegn W Kifle·Mumtaz Y Balkhi·Yasuko Ono·Jenn Davis·Naoko Doi·Aryandra Arya·Jiho Kim·Aravindan Kalyanasundaram·Sourav Nandy·Njariharinjakamampionona Rakotozandrindrainy·Bart Staker·Justin Craig·Raphaël Rakotozandrindrainy·Birkneh T Tadesse·Florian Marks·Lisa Jackson·Darrick Carter·Sean A Gray·Afzal A Siddiqui
View original source ↗Export metadata ↓

Abstract

An estimated 200 million people are currently infected with schistosomiasis and an additional 800 million reside in high transmission-risk areas in 78 endemic countries. In this report we describe a functional enzymatic assay based on the core calpain antigen (Sm-p80) of the schistosomiasis vaccine, SchistoShield®. A 44 kDa soluble variant of the core Sm-p80 antigen (B7), was assessed for its enzymatic activity using a fluorescent synthetic substrate. Inhibition of the B7 enzymatic activity by Sm-p80-specific antibodies obtained from pre-clinical trials in rodents, non-human primates as well as from participants of the human clinical trials was measured. The B7 enzyme activity followed a Michaelis-Menten-like kinetic behavior. Statistically significant inhibition of the B7 activity was observed by Sm-p80-specific antibodies produced by immunized mice, non-human primates and humans. This quantitative serological assay could be of value in assessing the effectiveness of the SchistoShield® vaccine in human trials in Africa.

Explore related subjects

Journal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Desalegn W Kifle, Mumtaz Y Balkhi, Yasuko Ono, Jenn Davis, Naoko Doi, Aryandra Arya, Jiho Kim, Aravindan Kalyanasundaram, Sourav Nandy, Njariharinjakamampionona Rakotozandrindrainy, Bart Staker, Justin Craig, Raphaël Rakotozandrindrainy, Birkneh T Tadesse, Florian Marks, Lisa Jackson, Darrick Carter, Sean A Gray, Afzal A Siddiqui. 2025-03-13. A functional enzymatic assay as potential readout for a clinical trial of a schistosomiasis vaccine.. https://doi.org/10.1038/s41541-024-01044-2

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2027

Effectiveness of high-dose versus standard-dose influenza vaccines against hospitalisation according to frailty risk: a prespecified analysis of the randomised trial DANFLU-2.

BACKGROUND: Frailty is a major risk factor for influenza-related complications and can influence vaccine effectiveness. We aimed to assess the relative vaccine effectiveness (rVE) of high-dose (HD-IIV) versus standard-dose inactivated influenza vaccine (SD-IIV) in older adults aged 65 years or older according to frailty risk. METHODS: This study was a prespecified analysis of DANFLU-2, an open-label, individually randomised trial, conducted in Denmark during three consecutive influenza seasons (2022-23, 2023-24, and 2024-25). Adults aged 65 years or older were randomised (1:1) to the HD-IIV or SD-IIV group. The primary endpoint was hospitalisation for influenza or pneumonia. Frailty was defined according to the validated Hospital Frailty Risk Score (HFRS) based on ICD-10 codes within 10 years before randomisation. Participants were stratified into three HFRS categories, namely low (<5 points), intermediate (5-15 points), and high (>15 points) frailty risk. The rVE of HD-IIV versus SD-IIV against the primary endpoint was assessed across prespecified HFRS categories and treating HFRS as a continuous variable. Pearson's chi-square test was used to compare safety events across frailty risk groups and randomisation groups. FINDINGS: Among 332&#x2009;438 randomised participants (mean age 73&#xb7;7 years [SD 5&#xb7;8]; 161&#x2009;538 [48&#xb7;6%] were female), 276&#x2009;173 (83&#xb7;1%) had low frailty risk, 52&#x2009;395 (15&#xb7;8%) had intermediate frailty risk, and 3861 (1&#xb7;2%) had high frailty risk. The primary endpoint of hospitalisation for influenza or pneumonia occurred in 1424 (0&#xb7;5%) of 276&#x2009;173 participants with low frailty risk, 761 (1&#xb7;5%) of 52&#x2009;395 with intermediate frailty risk, and 163 (4&#xb7;2%) of 3861 with high frailty risk (relative risk [RR] for intermediate vs low frailty risk 2&#xb7;8 [95% CI 2&#xb7;6-3&#xb7;1]; RR for high vs low frailty risk 8&#xb7;2 [7&#xb7;0-9&#xb7;6]). HFRS as a continuous variable significantly modified the effect of HD-IIV versus SD-IIV against the primary endpoint with higher rVE estimates with increasing HFRS (pinteraction=0&#xb7;020). The rVE was 0&#xb7;2% (95% CI -10&#xb7;8 to 10&#xb7;2) among those with low frailty risk, 13&#xb7;1% (-0&#xb7;4 to 24&#xb7;8) among those with intermediate frailty risk, and 19&#xb7;9% (-10&#xb7;3 to 42&#xb7;1) among those with high frailty risk. No significant interaction was observed when HFRS was assessed according to the prespecified categorical frailty groups (pinteraction=0&#xb7;17). The proportion of participants with at least one serious adverse event increased across frailty risk groups (13&#x2009;366 [4&#xb7;8%] of 275&#x2009;795 for low frailty risk, 5475 [10&#xb7;5%] of 52&#x2009;315 for intermediate frailty risk, and 777 [20&#xb7;2%] of 3850 for high frailty risk; p<0&#xb7;0001), with similar proportions of serious adverse events in the HD-IIV and SD-IIV groups for each frailty risk group. INTERPRETATION: Among adults aged 65 years or older in Denmark, frailty risk might modify the effects of HD-IIV versus SD-IIV against hospitalisation for influenza or pneumonia, with higher rVE estimates with increasing frailty risk. These findings might support considering high-dose influenza vaccines for frail older adults. However, effect modification was not evident when frailty was assessed using prespecified categorical subgroups, and subgroup-specific estimates were imprecise, with 95% CIs crossing the null. These results should be considered exploratory, warranting further investigation. FUNDING: The DANFLU-2 trial was funded by Sanofi.

Journal Article↗