Development and Evaluation of a Recombinant YidR Protein Vaccine against Klebsiella pneumoniae.pptx

Vaccination is a promising approach to prevent Klebsiella infection; however, the high heterogeneity of
strains is a limiting factor. The best antigenic target for an anti-Klebsiella vaccine should be expressed
by all or most of strains. We previously found YidR protein to be highly conserved among K. pneumoniae
strains independently of antigen serotype. Therefore, in the present study, we developed a recombinant
YidR protein vaccine and evaluated its protective efficacy against lethal challenge with K. pneumoniae in a
mouse model. The yidR gene was cloned in Escherichia coli for recombinant expression. The lethal dose
(LD100) of K. pneumoniae was determined and lethal challenge was carried out after immunization with
recombinant purified YidR. After immunization, the concentration of total serum IgG was significantly
higher in YidR-immunized mice than in non-immunized mice, indicating strong induction of antibodies.
Mice were challenged with LD100 of K. pneumoniae, and significantly lower murine sepsis and higher body
weight were observed in YidR-immunized mice compared to unvaccinated controls. Moreover, 90% of
YidR-immunized mice survived beyond 10 days of observation, whereas none of the control mice sur-
vived past 48 h. The protective effect of YidR recombinant protein vaccine was demonstrated and YidR
may be a promising vaccine candidate to prevent klebsiellos

1. Development and Evaluation of a Recombinant YidR Protein Vaccine against Klebsiella pneumoniae Joshua Idoko [email protected]

2. Contents 1. Introduction 2. Klebsiella pneumoniae Overview 3. Research Aim and Objectives 4. Study Methodology 5. Study Results 6. Discussion and Implications 7. Conclusion

3. Introduction Vaccination is a promising approach to prevent Klebsiella infection. The best antigenic target should be expressed by most strains. The YidR protein was found to be highly conserved among K. pneumoniae strains. This study developed a recombinant YidR protein vaccine and evaluated its protective efficacy against K. pneumoniae in a mouse model.

4. Klebsiella pneumoniae Overview Klebsiella pneumoniae is a gram-negative, encapsulated bacterium of the Enterobacteriaceae family. It is resilient, able to evade and suppress the immune system and grow at various host sites. The high prevalence of drug-resistant strains has become a significant public health concern. Treatment with antibiotics may have limited efficacy.

5. Research Aim and Objectives The aim was to develop a new recombinant protein vaccine for K. pneumoniae infection based on the YidR protein. Objectives included cloning the yidR gene in E. coli, determining the lethal dose of K. pneumoniae, and evaluating the vaccine's protective efficacy in a mouse model.

6. Study Methodology Research Methods Ethics Statement The study was conducted at Cornell University adhering to approved guidelines. 1 Protein Production The yidR gene was cloned, expressed, and purified from E. coli. 2 Lethal Dose Determination LD100 of K. pneumoniae was established using mouse models. 3 Immunization and Challenge Study Mice were immunized with YidR, followed by a lethal challenge with K. pneumoniae. 4

7. Study Results Key Findings Protein Production YidR protein was successfully expressed and purified. Lethal Dose Findings 4x10^7 CFU of K. pneumoniae was established as the LD100. Survival Rates 92.3% of immunized mice survived the lethal challenge, compared to 0% in the control group. Antibody Response Immunized mice had significantly higher serum IgG levels.

8. Discussion and Implications The vaccine induced a strong antibody response and significantly improved survival rates in mice. YidR is a promising target antigen for vaccine development against K. pneumoniae. Given the high conservation of YidR among strains, it holds potential for cross-protection against other gram-negative bacteria. Further studies in additional models and contexts are needed to validate these findings.

9. Conclusion The recombinant YidR protein vaccine showed significant protective efficacy against K. pneumoniae in a mouse model. This suggests YidR as a novel and promising candidate for vaccine development. Further research is recommended to explore its potential in other settings.