Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes

Autor: Simona Rondini, Gianmarco Gasperini, Laura B. Martin, Renzo Alfini, Maria Grazia Aruta, Francesca Mancini, Allan Saul, Rino Rappuoli, Francesca Necchi, Francesca Micoli, Omar Rossi, Francesco Citiulo
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Bacterial Diseases
Serotype
Physiology
RC955-962
Pathology and Laboratory Medicine
medicine.disease_cause
Biochemistry
Cross-reactivity
Shigella flexneri
Mice
Medical Conditions
Shigella Vaccines
Immune Physiology
Arctic medicine. Tropical medicine
Medicine and Health Sciences
Public and Occupational Health
Shigella
Shigella vaccine
Cross Reactivity
Vaccines
Immune System Proteins
Bacterial Gastroenteritis
O Antigens
Antibodies
Bacterial
Vaccination and Immunization
Bacterial Pathogens
Body Fluids
Gastroenteritis
Blood
Infectious Diseases
Medical Microbiology
Shigellosis
Female
Rabbits
Pathogens
Anatomy
Antibody
Public aspects of medicine
RA1-1270
Research Article
Neglected Tropical Diseases
Infectious Disease Control
Immunology
Shigella sonnei
Gastroenterology and Hepatology
Cross Reactions
Biology
Serogroup
Microbiology
Antibodies
Antigen
Vaccine Development
medicine
Animals
Humans
Antigens
Microbial Pathogens
Dysentery
Bacillary
Bacteria
Organisms
Public Health
Environmental and Occupational Health
Biology and Life Sciences
Proteins
Blood Serum
biochemical phenomena
metabolism
and nutrition
Tropical Diseases
medicine.disease
biology.organism_classification
Virology
digestive system diseases
biology.protein
bacteria
Preventive Medicine
Immune Serum
Zdroj: PLoS Neglected Tropical Diseases, Vol 15, Iss 10, p e0009826 (2021)
PLoS Neglected Tropical Diseases
ISSN: 1935-2735
1935-2727
Popis: No vaccine to protect against an estimated 238,000 shigellosis deaths per year is widely available. S. sonnei is the most prevalent Shigella, and multiple serotypes of S. flexneri, which change regionally and globally, also cause significant disease. The leading Shigella vaccine strategies are based on the delivery of serotype specific O-antigens. A strategy to minimize the complexity of a broadly-protective Shigella vaccine is to combine components from S. sonnei with S. flexneri serotypes that induce antibodies with maximum cross-reactivity between different serotypes. We used the GMMA-technology to immunize animal models and generate antisera against 14 S. flexneri subtypes from 8 different serotypes that were tested for binding to and bactericidal activity against a panel of 11 S. flexneri bacteria lines. Some immunogens induced broadly cross-reactive antibodies that interacted with most of the S. flexneri in the panel, while others induced antibodies with narrower specificity. Most cross-reactivity could not be assigned to modifications of the O-antigen, by glucose, acetate or phosphoethanolamine, common to several of the S. flexneri serotypes. This allowed us to revisit the current dogma of cross-reactivity among S. flexneri serotypes suggesting that a broadly protective vaccine is feasible with limited number of appropriately selected components. Thus, we rationally designed a 4-component vaccine selecting GMMA from S. sonnei and S. flexneri 1b, 2a and 3a. The resulting formulation was broadly cross-reactive in mice and rabbits, inducing antibodies that killed all S. flexneri serotypes tested. This study provides the framework for a broadly-protective Shigella vaccine which needs to be verified in human trials.
Author summary A strategy to optimize the composition for a broadly-protective Shigella vaccine is to combine components directed against S. sonnei with S. flexneri serotypes to induce antibody responses with the maximum cross-reactivity between different serotypes. Based on mouse and rabbit immunogenicity, we selected 4 GMMA-immunogens, derived from S. sonnei and S. flexneri 1b, 2a and 3a, able to induce antibodies that were broadly bactericidal against most epidemiologically significant S. flexneri strains in mice and rabbits. This was not predicted on the basis of O-antigen modifications conferring serotype or group specificities and allowed revisiting the dogma of cross-protection among S. flexneri serotypes. Overall, this study provides a framework for the rational design of a broadly-protective vaccine that will be evaluated in upcoming human vaccine trials. It also tackles a key issue regarding Shigella vaccine development that is balancing a sufficient number of antigenic components in the vaccine to provide adequate coverage of serotype diversity while minimizing complexity.
Databáze: OpenAIRE
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