High-Throughput IgG Epitope Mapping of Tetanus Neurotoxin: Implications for Immunotherapy and Vaccine Design

Abstract

Background: Tetanus is an acute, fatal disease caused by exotoxins released from Clostridium tetani during infections. A protective humoral immune response can be induced by vaccinations with pediatric and booster combinatorial vaccines that contain inactivated tetanus neurotoxin (TeNT) as a major antigen. Although some epitopes in NeNT have been described using various ap-proaches, a comprehensive list of its antigenic determinants that are involved with immunity have not been elucidated. To that end, a high resolution analysis of the linear B-cell epitopes in NeNT was performed using antibodies generated in vaccinated children. Methods: Two hundred sixty-four peptides that cover the entire coding sequence of TeNT protein were prepared in situ on a cellulose membrane by SPOT synthesis and probed with sera from children vaccinated (ChVS) with a triple DTP-vaccine to map continuous B-cell epitopes that were further characterized and validated by immunoassays. Results: Forty-three IgG epitopes were identified. Four (TT-215-218) were chemically synthesized as Multiple Antigen Peptides (MAPs) and used in peptide ELISAs to screen post-pandemic DTP vaccinations. The assay displayed a high performance with high sensitivity (99.99%) and specificity (100%). Conclusions: The complete map of linear IgG epitopes induced by vaccination with inactivated TeNT highlights three key epitopes involved in the ef-ficacy of the vaccine. Antibodies against epitope TT-8/G can block enzymatic activity, and those against epitopes TT-40/G and TT-42/G can interfere with TeNT binding to neuronal cell receptors. We further show that four of the epitopes identified can be employed in peptide ELISAs to assess vaccine coverage. Overall, the data suggest a set of select epitopes to engineer new, directed vaccines

Perfil epidemiológico do Tétano acidental no Brasil entre 2012 e 2022

“…6 É importante ressaltar que a análise do presente estudo não engloba o tétano neonatal são usualmente separadas devido a diferentes aspectos epidemiológicos relacionados a cada um, apesar da semelhança fisiopatológica. 7 Apesar dessa tendência, no recorte temporal analisado, a incidência do tétano acidental se manteve relativamente estável, em consonância com outras análises recentes 8 , no entanto, com visível redução nos anos de 2020 e 2021, indicando uma possível menor exposição devido ao isolamento social demandado pela pandemia do COVID-19 e em conformidade com uma tendência mundial nesse período segundo dados da OMS 9 , havendo no entanto uma redução de mais de 10% na letalidade (de 33,7% a 22,9%) . Apesar disso, foi vista uma progressiva redução da letalidade, evidenciando uma possível maior eficácia e acesso ao tratamento dessa patologia.…”