A Threat From Within
Candida albicans is a pathogenic yeast species that is naturally occurring in the mouth and the digestive system. Overproduction of C. albicans results in a range of infections such as vaginal candidiasis—more commonly known as yeast infection—and invasive candidiasis, which has a high mortality and morbidity rate of approximately 60%. Its invasion is mediated by the agglutinin-like sequence protein 3 (Als3), which allows C. albicans to bind to the cells of its host. The primary means of treating fungal infections such as C. albicans is via antifungals like azoles and polyenes to which yeast strains can develop resistance towards (Kaur et al., 2023).
Other conventional forms of treatment also have their shortcomings. Many widespread vaccines, such as the flu shot or the Tdap vaccine, rely on inactivated or killed bacteria to provoke an immune response and prepare the body to fight infections in the future. However, the development of such vaccines can be a slow process, especially considering the long and costly cultivation and maintenance of inactivated bacteria. Furthermore, many vaccines require multiple injections in order to produce an optimal immune response, which begs the question of the efficacy of this type of treatment (Kumar & Kumar, 2019). As a result, researchers are considering alternative routes of vaccine development in order to make such treatments accessible and affordable.
Bread as a Bodyguard
A promising avenue is through the engineering of Saccharomyces cerevisiae—also known as Baker’s Yeast. Due to its widespread use in baking and brewery and nontoxicity, S. cerevisiae is a model organism for genetic engineering. In other words, the plasmid, or DNA sequence, of this yeast can be altered to express proteins with high therapeutic potential, meaning they can effectively combat the virus without many harmful side effects. This modification in the genomic sequence will in turn optimize the transcription and translation process, thereby resulting in the high expression of a desired protein.
Agglutinin-like sequence protein 3 is a protein that is expressed by both C. albicans and S. cerevisiae, and it possesses immunogenic properties when it is produced in high quantities (Alqarihi et al., 2019). Truly this protein can act as an antigen, or foreign body, and thus trigger an immune response in order to build antibodies against Candidiasis. By presenting Als3 to the immune system, the body generates a memory response that enables the immune system to quickly recognize and respond to Candidiasis during subsequent exposures, thereby protecting against any future infections.
The immunogenicity of Als3 has already been tested in mice. When recombinant,or genetically engineered,S. cerevisiae is administered, antibodies against Als3 were produced, thereby preventing the attachment and colonization of C. albicans. In fact, mice treated with the vaccine administered to their jugular vein were significantly more protected from C. albicans infection and had less fungal growth than control mice (Alqarihi et al., 2019). With this evidence, Als3 can be considered a promising avenue for vaccine development against a prolific and intimidating infection.
References
Alqarihi, A., Singh, S., Edwards, J. E., Ibrahim, A. S., & Uppuluri, P. (2019). NDV-3A vaccination prevents C. albicans colonization of jugular vein catheters in mice. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-42517-y
Kaur, G., Chawla, S., Kumar, P., & Singh, R. (2023). Advancing Vaccine Strategies against Candida Infections: Exploring New Frontiers. Vaccines, 11(11), 1658. https://doi.org/10.3390/vaccines11111658
Kumar, R., & Kumar, P. (2019). Yeast-based vaccines: New perspective in vaccine development and application. FEMS Yeast Research, 19(2). https://doi.org/10.1093/femsyr/foz007
Singh, S., Nabeela, S., Barbarino, A., Ibrahim, A. S., & Uppuluri, P. (2022). Antibodies targeting Candida albicans Als3 and Hyr1 antigens protect neonatal mice from candidiasis. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.925821