Harnessing antifungal immunity in pursuit of a Staphylococcus aureus vaccine strategy

Abstract

Staphylococcus aureus ( S . aureus ) is one of the most common bacterial infections worldwide, and antibiotic resistant strains such as Methicillin-Resistant S . aureus (MRSA) are a major threat and burden to public health. MRSA not only infects immunocompromised patients but also healthy individuals and has rapidly spread from the healthcare setting to the outside community. However, all vaccines tested in clinical trials to date have failed. Immunocompromised individuals such as patients with HIV or decreased levels of CD4 + T cells are highly susceptible to S . aureus infections, and they are also at increased risk of developing fungal infections. We therefore wondered whether stimulation of antifungal immunity might promote the type of immune responses needed for effective host defense against S . aureus . Here we show that vaccination of mice with a fungal β-glucan particle (GP) loaded with S . aureus antigens provides protective immunity to S . aureus . We generated glucan particles loaded with the four S . aureus proteins ClfA, IsdA, MntC, and SdrE, creating the 4X-SA-GP vaccine. Vaccination of mice with three doses of 4X-SA-GP promoted protection in a systemic model of S . aureus infection with a significant reduction in the bacterial burden in the spleen and kidneys. 4X-SA-GP vaccination induced antigen-specific Th1 and Th17 CD4 + T cell and antibody responses and provided long-term protection. This work suggests that the GP vaccine system has potential as a novel approach to developing vaccines for S . aureus .

Determination of nasal carriage and skin colonization, antimicrobial susceptibility and genetic relatedness of Staphylococcus aureus isolated from patients with atopic dermatitis in Szczecin, Poland

“…It's important to underline that antimicrobial therapy should be considered only in exacerbation of AD symptoms and complications following multiple and recurrent bacterial skin infections. The immunization with autovaccines composed of unique S. aureus antigens that aim the skin beneficial bacteria remain unharmed, is considered as an alternative in AD management [59][60][61].…”

History and Perspective of Immunotherapy for Pythiosis

“…These drawbacks impede the use of this model in the evaluation of PIA immunotherapy. On the other hand, the mouse is a well-studied model for the immunological study of many infectious diseases [265][266][267]. Reproduction of the P. insidiosum infection in mice is possible but requires pre-treatment with an immunosuppressive agent (i.e., cyclophosphamide) [251,268,269], making this versatile animal model less suitable for the PIA assessment.…”

Therapeutic and Industrial Applications of Curdlan With Overview on Its Recent Patents

“…Protective immunity to Staphylococcus aureus was observed by vaccination of mice with fungal β-glucan particles (GP) loaded with S. aureus antigens. The findings suggest that the glucan particles vaccine system has the potential as a novel approach for developing vaccines against S. aureus ( 72 ). Chemo- and radio-therapies cause several side effects in patients with cancer.…”