Vaccine that harnesses antifungal immunity protects mice from staph infection

Immunization of mice with a new vaccine consisting of fungal particles loaded with Staphylococcus aureus (S. aureus) proteins protects mice against S. aureus infection, according to a study published August 20 2020 in the open-access journal PLOS Pathogens by David Underhill of Cedars-Sinai Medical Center, and colleagues.

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. Vaccines aimed at targeting S. aureus have failed in clinical trials, and the reason for this lack of success remains unclear. As this pathogen continues to rapidly spread on a global scale, it is vital that new approaches to S. aureus vaccination are developed. Immunocompromised individuals such as patients with HIV are highly susceptible to S. aureus infections, and they are also at increased risk of developing fungal infections. Based on this evidence, Underhill and colleagues tested whether stimulation of antifungal immunity would promote the type of immune responses needed for effective host defense against S. aureus.

The researchers developed a new vaccine called 4X-SA-GP, which consists of fungal β-glucan particles loaded with four S. aureus proteins. Mice were vaccinated once a week for three weeks with 4X-SA-GP, and then injected with S. aureus either four or eight weeks later. Vaccination induced protective T cell and antibody responses, and the T cell responses in particular were essential for vaccine-induced protection from S. aureus infection. Moreover, the mice had detectable antibody levels and reduced S. aureus levels in the spleen and kidneys eight weeks after immunization. According to the authors, this work potentially broadens the use of the β-glucan particle vaccine system for a much-needed vaccine targeting S. aureus.

The authors conclude, “We need some creative new approaches to explore towards developing a S. aureus vaccine, and we are excited to share our recent experiences with antigen-loaded fungal particles”.

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Peer-reviewed; Experimental study; Animals

Funding: The study was supported by the National Institutes of Health (https://www.nih.gov/) grants R01 DK093426 (to D.M.U.) and R01 AI127406 (to D.M.U, G.Y.L., and G.A.M.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: Paterson MJ, Caldera J, Nguyen C, Sharma P, Castro AM, Kolar SL, et al. (2020) Harnessing antifungal immunity in pursuit of a Staphylococcus aureus vaccine strategy. PLoS Pathog 16(8): e1008733. https://doi.org/10.1371/journal.ppat.1008733

F. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, and the Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.

Division of Pediatric Infectious Diseases and Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.

Department of Medicine, Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.

Division of Infectious Diseases, Department of Pediatrics, UCSD, San Diego, California, United States of America.

In your coverage please use this URL to provide access to the freely available paper: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008733