Temporal trends in tetanus incidence and lethality in Brazil: analysis of the national database from 2009 to 2018

Carvalho, Larissa Chaves de; Marques, Consuelo Penha Castro; Rodrigues, Vandílson Pinheiro

doi:10.1590/1806-9282.20210736

Cited by 1 publication

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References 20 publications

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“…Despite the existence of a safe and low-cost vaccine, the lack of vaccination campaigns, booster doses, and variable response to vaccines due to an immunocompromised state or age mean that the incidence and mortality rate of tetanus are worrying [ 10 , 11 ]. In Brazil, the incidence rate decreased from 1.6 to 0.95 per million inhabitants in 2018, but lethality increased from 30.77 to 40.70%, mainly in the elderly and the northern regions [ 12 ]. Although tetanus is considered endemic in low- and middle-income countries, accounting for a significant mortality and disability rate in pregnant women, newborns, and the unimmunized or poorly immunized population [ 13 ], tetanus is everywhere, with 11,863 reported cases in 2020 (WHO).…”

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confidence: 99%

Characterization of Neutralizing Human Anti-Tetanus Monoclonal Antibodies Produced by Stable Cell Lines

et al. 2022

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Tetanus toxin (TeNT) is produced by C. tetani, a spore-forming bacillus broadly spread in the environment. Although an inexpensive and safe vaccine is available, tetanus persists because of a lack of booster shots and variable responses to vaccines due to immunocompromised status or age-decreased immune surveillance. Tetanus is most prevalent in low- and medium-income countries, where it remains a health problem. Neutralizing monoclonal antibodies (mAbs) can prevent the severity of illness and death caused by C. tetani infection. We identified a panel of mAbs that bind to TeNT, some of which were investigated in a preclinical assay, showing that a trio of mAbs that bind to different sites of TeNT can neutralize the toxin and prevent symptoms and death in mice. We also identified two mAbs that can impair the binding of TeNT to the GT1b ganglioside receptor in neurons. In this work, to generate a series of cell lines, we constructed vectors containing sequences encoding heavy and light constant regions that can receive the paired variable regions resulting from PCRs of human B cells. In this way, we generated stable cell lines for five mAbs and compared and characterized the antibody produced in large quantities, enabling the characterization experiments. We present the results regarding the cell growth and viability in a fed-batch culture, titer measurement, and specific productivity estimation. The affinity of purified mAbs was analyzed by kinetics and under steady-state conditions, as three mAbs could not dissociate from TeNT within 36,000 s. The binding of mAbs to TeNT was confirmed by ELISA and inhibition of toxin binding to GT1b. The use of the mAbs mixture confirmed the individual mAb contribution to inhibition. We also analyzed the binding of mAbs to FcγR by surface plasmon resonance (SPR) and the glycan composition. Molecular docking analyses showed the binding site of an anti-tetanus mAb.

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