#FEMSmicroBlog: Yeast to deliver nucleic acid-based vaccines

24-04-2021

Vaccination is an effective measure to control various infectious diseases that affect human and veterinary health. The most recent generation of vaccines comprises nucleic acids as antigens and as such, DNA or mRNA vaccines can efficiently induce the production of antibodies and mediate a cellular response promoting effective and safe protection. A new minireview in FEMS Yeast Research explores “Yeasts as a promising delivery platform for DNA and RNA vaccines“. In time for the World Immunization Week commencing on 24th April, corresponding author Antonio de Freitas explains for the #FEMSmicroBlog how yeasts are promising tools for vaccination strategies. #FascinatingMicrobes

 

Yeast as a promising delivery vehicle for nucleic acids

In the context of the SARS-CoV-2 pandemic, mRNA vaccines have been licensed for immunization programs in several countries around the world in an unprecedented way. mRNA-based vaccines have several advantages including the safety and induction of specific immune responses by activating B and T cells. Despite these features, stability and in vivo bioavailability are limited and reinforce the need for adjuvants and better delivery strategies.

The minireview “Yeasts as a promising delivery platform for DNA and RNA vaccines” published in FEMS Yeast Research outlines different whole yeast vaccine strategies as carriers of nucleic acids in the medical field, as well as immunological mechanisms of yeast-based vaccination strategies. It discusses how a yeast-based drug delivery platform can be applied in promoting effective immune responses for prophylactic and therapeutic approaches against infectious diseases, or in immunotherapies for different cancer types.

Yeast-based drug delivery platforms can be applied to trigger effective immune responses against infectious diseases or for immunotherapy.

Delivery of nucleic acids can occur via physical, chemical, or even biological means. Using yeast to carry nucleic acids is a promising tool as it presents several benefits such as the absence of toxicity, the adjuvant properties, the possibility of oral administration, and the specific delivery to professional antigen-presenting cells.

Yeasts species such as Saccharomyces cerevisiae and Pichia pastoris have been successfully used as host organisms to produce subunit vaccine antigens. In the last two decades, these organisms were also explored as vaccine vehicles to deliver antigens such as proteins and nucleic acids.

The employed species possess a GRAS status meaning they are “Generally Recognized as Safe”. As such, yeast organisms can be used to produce therapeutic proteins as they promote immuno-stimulation.

Mechanism of delivery of DNA and mRNA vaccines carried by yeasts through oral administration.
Mechanism of delivery of DNA and mRNA vaccines carried by yeasts through oral administration. From Duarte Silva et al. in FEMS Microbes (read the full article here).

 

Yeast-based drug delivery in diverse applications

Once administered to the host, macrophages or dendritic cells can phagocytose yeast cells. This uptake is stimulated by components of the yeast cell wall that have adjuvant properties and are recognized by pattern recognition receptors. Also, the yeast diameter (2–5 μm) is advantageous to trigger phagocytosis.

Notably, recombinant yeasts concentrate the antigens in “packages” to increase the number of antigens available for processing. This leads to avid internalisation by antigen-presenting cells resulting in a specific and efficient presentation for T cells.

Recombinant yeasts can also be used to modify the functional phenotypes of macrophages. This activates pro-inflammatory cytokines that are important for the success of anti-tumor therapies.

Some studies also applied yeast-based vehicles in immunotherapy by regulating target genes with interference RNAs. Such a platform was shown to carry sequence-specific short hairpin RNAs to silence key immunological mediators and receptors in immunotherapeutic strategies for auto-immune diseases and allergies.

 

About the author of this blog

Dr. Antonio de Freitas holds a Bachelor of Biological Sciences from UNESP – Universidade Estadual Paulista (Brazil); Master and PhD in Molecular Biology from UNIFESP – the Federal University of São Paulo (Brazil); Post-Doctorate in Vaccinology from Butantan Institute (Brazil); Associate Professor III, Department of Genetics, Federal University of Pernambuco (Brazil); CNPq Productivity 1C Scholarship Researcher.

About this blog section

The section #FascinatingMicrobes for the #FEMSmicroBlog explains the science behind a paper and highlights the significance and broader context of a recent finding. One of the main goals is to share the fascinating spectrum of microbes across all fields of microbiology.

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