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Enrichment of Native and Recombinant Extracellular Vesicles of Mycobacteria
Published on: December 8, 2023
Salmonella vaccines secreting measles virus epitopes induce protective immune responses against measles virus
S Spreng1, I Gentschev, W Goebel
1Lehrstuhl für Mikrobiologie, Theodor-Boveri-Institut für Biowissenschaften, Am Hubland, D-97074, Würzburg, Germany. simone@biozentrum.uni-wuerzburg.de
Abstract:
In the present study we describe a live vaccine against measles virus (MV) infection on the basis of attenuated Salmonella typhimurium aroA secreting MV antigens via the Escherichia coli alpha-hemolysin secretion system. Two well-characterized MV epitopes, a B-cell epitope of the MV fusion protein (amino acids 404-414) and a T-cell epitope of the MV nucleocapsid protein (amino acids 79-99) were fused as single or repeating units to the C-terminal secretion signal of the E. coli hemolysin and expressed in secreted form by the attenuated S. typhimurium aroA SL7207. Immunization of MV-susceptible C3H mice revealed that S. typhimurium SL7207 secreting these antigens provoked a humoral and a cellular MV-specific immune response, respectively. Mice vaccinated orally with a combination of both recombinant S. typhimurium strains showed partial protection against a lethal MV encephalitis after intracerebral challenge with a rodent-adapted, neurotropic MV strain.
Insights
This study developed a live vaccine using attenuated Salmonella typhimurium to deliver measles virus (MV) antigens. Oral vaccination in mice induced immune responses and offered partial protection against MV encephalitis.
Area of Science:
- * Vaccinology and immunology
- * Microbial genetics and molecular biology
Background:
- * Measles virus (MV) infection poses a significant global health challenge, necessitating effective vaccine strategies.
- * Current vaccines are effective but require cold chain maintenance and administration by healthcare professionals.
- * Development of novel, orally administered live vaccines could improve accessibility and efficacy.
Purpose of the Study:
- * To engineer an attenuated Salmonella typhimurium strain to secrete key measles virus antigens.
- * To evaluate the immunogenicity and protective efficacy of this novel vaccine candidate in a mouse model.
Main Methods:
- * Construction of recombinant Salmonella typhimurium aroA (SL7207) secreting MV B-cell and T-cell epitopes using the E. coli alpha-hemolysin secretion system.
- * Oral immunization of C3H mice with single or combined recombinant S. typhimurium strains.
- * Assessment of MV-specific humoral and cellular immune responses.
- * Evaluation of protection against lethal MV encephalitis following intracerebral challenge.
Main Results:
- * Recombinant S. typhimurium successfully secreted MV antigens, eliciting both humoral and cellular MV-specific immune responses in immunized mice.
- * Oral vaccination with a combination of the recombinant strains conferred partial protection against a neurotropic MV strain challenge.
- * The vaccine candidate demonstrated potential for inducing protective immunity against measles virus.
Conclusions:
- * Attenuated Salmonella typhimurium secreting MV antigens represents a promising platform for a live, orally administered measles vaccine.
- * The developed vaccine candidate induced measurable immune responses and partial protection, warranting further investigation.
- * This approach may offer a more accessible and potentially more effective strategy for measles prevention.
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