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Development of safe, effective and immunogenic vaccine candidate for diarrheagenic Escherichia coli main pathotypes
Asmaa Gohar1, Nourtan F Abdeltawab2, Ali Fahmy3,4
1Viral Control Unit, National Organization of Research and Control of Biological, Cairo, Egypt. asma.gohar@yahoo.com.
Insights
A new low-cost vaccine combining five diarrheagenic Escherichia coli (E. coli) pathotypes offers protection and elicits a strong immune response in mice. This is the first combined vaccine candidate against the five main E. coli pathotypes, showing promise for human trials.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Enteric and diarrheal diseases cause over 750,000 childhood deaths annually, with diarrheagenic Escherichia coli (E. coli) being a major contributor.
- Current vaccines target only one or two of the five main diarrheagenic E. coli pathotypes, leaving a gap in broad-spectrum protection.
- The development of a cost-effective, multi-pathotype vaccine is crucial for reducing childhood mortality in developing regions.
Purpose of the Study:
- To develop a novel, low-cost vaccine candidate combining the five main diarrheagenic E. coli pathotypes for wide-spectrum protection.
- To evaluate the efficacy and immunogenicity of this combined vaccine in a preclinical mouse model.
Main Methods:
- A formalin-killed whole-cell vaccine was formulated using a mixture of enteroaggregative, enteropathogenic, enteroinvasive, enterohemorrhagic, and enterotoxigenic E. coli pathotypes.
- Balb/C mice were immunized subcutaneously and subsequently challenged with E. coli to assess survival rates.
- Immunological responses, including specific systemic antibodies (IgG), interferon gamma (IFNγ), and interleukin 6 (IL-6) levels, were monitored over six weeks. Adjuvant systems (alum and cholera toxin B subunit - CTB) were also evaluated.
Main Results:
- The combined vaccine candidate demonstrated 100% survival in mice post-challenge compared to unimmunized controls.
- Significant increases in specific IgG, IFNγ, and IL-6 levels were observed in mice immunized with the combined vaccine, particularly within the first two weeks.
- The CTB-adjuvanted combined vaccine showed superior IgG and IFNγ responses compared to the alum-adjuvanted formulation.
Conclusions:
- The developed combined vaccine candidate provides protection against the five main diarrheagenic E. coli pathotypes in a single formulation.
- This represents the first cost-effective, combined vaccine against these five pathotypes, demonstrating significant promise for further preclinical and clinical development.
- The findings support the potential of this vaccine to offer broad-spectrum protection against a major cause of childhood diarrheal disease.
Background:
Enteric and diarrheal diseases are important causes of childhood death in the developing world. These diseases are responsible for more than 750 thousand deaths in children under 5 years old worldwide, ranking second cause of death, after lower respiratory diseases, in this age group. Among the major causative agents of diarrhea is Escherichia coli. There are several vaccine trials for diarrheagenic E. coli. However, diarrheagenic E. coli has seven pathotypes and vaccines are directed for one or two of the five main pathotypes-causing diarrhea. Currently, there are no combined vaccines available in the market for all five diarrheagenic E. coli pathotypes. Therefore, we aimed to develop a low-cost vaccine candidate combining the five main diarrheagenic E. coli to offer wide-spectrum protection. We formulated a formalin-killed whole-cell mixture of enteroaggregative, enteropathogenic, enteroinvasive, enterohemorrhagic, and enterotoxigenic E. coli pathotypes as a combined vaccine candidate.
Results:
We immunized Balb/C mice subcutaneously with 10(9) CFU of combined vaccine candidate and found a significant increase in survival rate post challenge compared to unimmunized controls (100 % survival). Next we aimed to determine the immunological response of mice to the combined vaccine candidate compared to each pathotype immunization. To do so, we immunized mice groups with combined vaccine candidate and monitored biomarkers levels over 6 weeks as well as measured responses post challenge with relevant living E. coli. We found significant increase in specific systemic antibodies (IgG), interferon gamma (IFNγ) and interleukin 6 (IL-6) levels elicited by combined vaccine candidate especially in the first 2 weeks after mice immunization compared to controls (p < 0.05). We also evaluated alum and cholera toxin B subunit (CTB) as potential adjuvant systems for our candidate vaccine. We found that CTB-adjuvanted combined vaccine candidate showed significantly higher IgG and IFNγ levels than alum.
Conclusions:
Overall, our combined vaccine candidate offered protection against the five main diarrheagenic E. coli pathotypes in a single vaccine using mouse model. To the best of our knowledge, this is the first combined vaccine against the five main diarrheagenic E. coli pathotypes that is cost-effective with promise for further testing in humans.
