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- Multi-country and intersectoral assessment of cluster congruence between pipelines for genomics surveillance of foodborne pathogensPublication . Mixão, Verónica; Pinto, Miguel; Brendebach, Holger; Sobral, Daniel; Santos, João Dourado; Radomski, Nicolas; Uldall, Anne Sophie Majgaard; Bomba, Arkadiusz; Pietsch, Michael; Bucciacchio, Andrea; de Ruvo, Andrea; Castelli, Pierluigi; Iwan, Ewelina; Simon, Sandra; Coipan, Claudia E.; Linde, Jörg; Petrovska, Liljana; Kaas, Rolf Sommer; Joensen, Katrine Grimstrup; Nielsen, Sofie Holtsmark; Kiil, Kristoffer; Lagesen, Karin; Di Pasquale, Adriano; Gomes, João Paulo; Deneke, Carlus; Tausch, Simon H.; Borges, VítorDifferent laboratories employ different Whole-Genome Sequencing (WGS) pipelines for Food and Waterborne disease (FWD) surveillance, casting doubt on the comparability of their results and hindering optimal communication at intersectoral and international levels. Through a collaborative effort involving eleven European institutes spanning the food, animal, and human health sectors, we aimed to assess the inter-pipeline clustering congruence across all resolution levels and perform an in-depth comparative analysis of cluster composition at outbreak level for four important foodborne pathogens: Listeria monocytogenes, Salmonella enterica, Escherichia coli, and Campylobacter jejuni. We found a general concordance between allele-based pipelines for all species, except for C. jejuni, where the different resolution power of allele-based schemas led to marked discrepancies. Still, we identified non-negligible differences in outbreak detection and demonstrated how a threshold flexibilization favors the detection of similar outbreak signals by different laboratories. These results, together with the observation that different traditional typing groups (e.g., serotypes) exhibit a remarkably different genetic diversity, represent valuable information for future outbreak case-definitions and WGS-based nomenclature design. This study reinforces the need, while demonstrating the feasibility, of conducting continuous pipeline comparability assessments, and opens good perspectives for a smoother international and intersectoral cooperation towards an efficient One Health FWD surveillance.
- The impact of orthopoxvirus vaccination and Mpox infection on cross-protective immunity: a multicohort observational studyPublication . Crandell, Jameson; Pischel, Lauren; Fang, Zhenhao; Conde, Luciana; Zhong, Yi; Lawres, Lauren; Meira de Asis, Gustavo; Maciel, Gabriela; Zaleski, Agnieszka; Lira, Guilherme S.; Higa, Luiza M.; Breban, Mallery I.; Vogels, Chantal B.F.; Caria, João; Pinto, Ana Raquel; Almeida, Vasco; Maltez, Fernando; Cordeiro, Rita; Póvoas, Diana; Grubaugh, Nathan D.; Aoun-Barakat, Lydia; Grifoni, Alba; Sette, Alessandro; Castineiras, Terezinha M.; Chen, Sidi; Yildirim, Inci; Vale, Andre M.; Omer, Saad B.Background: Cross-reactive immune memory responses to orthopoxviruses in humans remain poorly characterised despite their relevance for vaccine design and outbreak control. We aimed to assess the magnitude, specificity, and durability of cross-reactive immune responses elicited by smallpox vaccines and mpox virus infection. Methods: We did a multicohort observational study involving participants from the USA, Brazil, and Portugal across four groups: Dryvax (first-generation smallpox vaccine) recipients vaccinated 40-80 years ago, JYNNEOS (third-generation smallpox vaccine) recipients vaccinated within the past year, a cohort receiving both vaccines, and patients infected with clade IIb mpox. Samples were analysed for systemic and mucosal humoral responses, neutralising antibody titres, viral antigen structural analysis, and T-cell cross-reactivity to vaccina virus, cowpox virus, and mpox virus. Statistical analyses included correlation assessments and comparisons across cohorts to determine the magnitude, longevity, and breadth of immune responses. Findings: Between July 7, 2022, and Aug 3, 2023, 262 participants were recruited, resulting in analysis of 378 samples. Both first-generation and third-generation smallpox vaccines elicited vaccinia virus-reactive and mpox virus-reactive antibodies, with the strongest responses targeting the less conserved extracellular virion antigens B5 and A33. Despite high concentrations of anti-mpox virus antibodies in the plasma, cross-neutralisation activity correlated with viral antigenic distance. Higher neutralisation was observed for cowpox virus than for mpox virus, which has lower antigenic conservation with vaccina virus. Complement-mediated neutralisation enhanced mpox virus neutralisation, overcoming the limitations of antigenic distance. Dryvax recipients sustained vaccina virus neutralisation titres for over 80 years, whereas cross-reactive responses did not show this durability. JYNNEOS-induced responses waned within a year. T-cell cross-reactivity was long-lasting, detected up to 70 years after vaccination. Booster vaccinations augmented the magnitude, breadth, and longevity of cross-neutralising responses. Interpretation: Our findings highlight the potential combined role of antibody effector functions and T-cell memory in cross-protection against orthopoxviruses. Complement-mediated neutralisation enhances cross-protection, overcoming antigenic distance. These Fc-mediated functions, along with T-cell responses, contribute to effective and long-lasting immunity conferred by smallpox vaccines against other orthopoxviruses.