Dual-antigen fusion protein vaccination induces protective immunity against infection in mice.

Hum Vaccin Immunother

National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, China.

Published: December 2024

AI Article Synopsis

  • A dual-antigen fusion protein vaccine (AH) targeting Als3 and Hyr1 proteins was developed to combat nosocomial bloodstream infections, especially in immunocompromised patients, using AlPO as an adjuvant.
  • In animal studies with mice and rabbits, the AH vaccine showed significant improvements in survival rates (80% for vaccinated mice) and higher antibody responses compared to controls, indicating strong immunogenicity.
  • The vaccine also reduced fungal burdens in vital organs and decreased organ damage, while sera from rabbits exhibited antifungal activity, supporting further research into dual-antigen vaccine approaches.

Article Abstract

Is a leading cause of nosocomial bloodstream infections, particularly in immunocompromised patients. Current therapeutic strategies are insufficient, highlighting the need for effective vaccines. This study aimed to evaluate the efficacy of a dual-antigen fusion protein vaccine (AH) targeting the Als3 and Hyr1 proteins of , using AlPO as an adjuvant. The AH vaccine was constructed by fusing Als3 and Hyr1 proteins, and its immunogenicity was tested in BALB/c mice and New Zealand white rabbits. Mice received three intramuscular doses of the vaccine combined with AlPO, followed by a lethal challenge with SC5314. Survival rates, antibody responses, cytokine production, fungal burdens, and organ pathology were assessed. The vaccine's efficacy was also validated using rabbit serum. Mice vaccinated with the AH-AlPO combination exhibited significantly higher antibody titers, particularly IgG and its subclasses, compared to controls ( < .001). The survival rate of vaccinated mice was 80% post-infection, significantly higher than the control group ( < .01). Vaccinated mice showed reduced fungal loads in the blood, kidneys, spleen, and liver ( < .05). Increased levels of interferon gamma and interleukin (IL)-17A were observed, indicating robust T helper (Th) 1 and Th17 cell responses. Vaccination mitigated organ damage, with kidney and liver pathology scores significantly lower than those of unvaccinated mice ( < .05). Rabbit serum with polyclonal antibodies demonstrated effective antifungal activity, confirming vaccine efficacy across species. The AH-AlPO vaccine effectively induced strong immune responses, reduced fungal burden, and protected against organ pathology in infections. These findings support further development of dual-antigen vaccine strategies.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441037PMC
http://dx.doi.org/10.1080/21645515.2024.2406065DOI Listing

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