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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Vaccines and Molecular Therapeutics

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1652460

Antibodies elicited by altSonflex1-2-3 GMMA vaccine are bactericidal against a panel of drug-resistant Shigella clinical isolates

Provisionally accepted
Elena BoeroElena Boero1Roberta Di BenedettoRoberta Di Benedetto1Giacomo VezzaniGiacomo Vezzani1Renzo AlfiniRenzo Alfini1Pieter-Jan CeyssensPieter-Jan Ceyssens2Giannoula S. TansarliGiannoula S. Tansarli3Ferric C. FangFerric C. Fang3Carla FontanaCarla Fontana4Alberto RossiAlberto Rossi4Stefania CarraraStefania Carrara4Francesca ManciniFrancesca Mancini1Miren Iturriza-GómaraMiren Iturriza-Gómara1Claudia SalaClaudia Sala5Carlo GiannelliCarlo Giannelli1Omar RossiOmar Rossi1Francesca MicoliFrancesca Micoli1*
  • 1GSK Vaccines Institute for Global Health, Siena, Italy
  • 2Sciensano, Brussels, Belgium
  • 3University of Washington Department of Laboratory Medicine & Pathology, Seattle, United States
  • 4Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, Rome, Italy
  • 5Toscana Life Sciences Foundation, Siena, Italy

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Shigellosis significantly impacts global health, particularly affecting vulnerable populations in lowand middle-income countries, with over 270 million annual infections. It also causes morbidity in specific high-risk groups in high-income countries. Antibiotic treatment is increasingly compromised by multidrug-resistant strains, highlighting the urgent need for a Shigella vaccine. We have developed a 4-component O-antigen-based vaccine candidate targeting S. sonnei and S. flexneri 1b, 2a and 3a serotypes, named altSonflex1-2-3, to provide broad protection against most globally prevalent Shigella strains. Here we have characterized the O-antigen structural features of a panel of S. flexneri drug-resistant clinical isolates and verified that they did not significantly differ from OAg O-antigen in the vaccine. Preclinical sera elicited by altSonflex1-2-3 were bactericidal against most strains, confirming the ability of anti-OAg O-antigen antibodies to recognize and kill in vitro different clinical isolates. Importantly, our results suggest that altSonflex1-2-3 could offer protection against antimicrobial resistant Shigella strains, addressing a critical public health issue.

Keywords: Shigella, altSonflex1-2-3, Vaccine, AMR, O-antigen, Sba, GMMA

Received: 23 Jun 2025; Accepted: 04 Aug 2025.

Copyright: © 2025 Boero, Di Benedetto, Vezzani, Alfini, Ceyssens, Tansarli, Fang, Fontana, Rossi, Carrara, Mancini, Iturriza-Gómara, Sala, Giannelli, Rossi and Micoli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Francesca Micoli, GSK Vaccines Institute for Global Health, Siena, Italy

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material