Oral Immunization with Yeast-Surface Display of SARS-CoV-2 Antigens in Pichia pastoris Induces Humoral Responses in BALB/C Mice.

Abstract

Background/Objectives: The pandemic caused by SARS-CoV-2 boosted the development of different vaccine models. In parallel, yeasts stand out as a vaccine platform in healthcare biotechnology. Species such as Saccharomyces cerevisiae and Pichia pastoris can express heterologous proteins, which are capable of inducing specific antibodies and can perform as an attractive vaccine vehicle with immunomodulating properties due to their cell wall composition. Furthermore, the yeast surface display system facilitates antigen presentation to immune cells. We developed an oral vaccine based on P. pastoris displaying a synthetic antigen composed of Spike and Nucleocapsid epitopes. Methods: The vaccine was administered to BALB/c mice. Systemic immune response was measured through antibody detection in blood samples, and mucosal immunity was assessed via IgA levels in feces. Histopathological analysis of intestinal and gastric tissues was also conducted. Results: The yeast-based vaccine elicited a humoral immune response, reflected in the production of neutralizing antibodies and elevated levels of IgG2a and IgG2. No structural alterations or pathological changes were observed in gastrointestinal tissues. Conclusions: This study demonstrates the feasibility of using P. pastoris as an oral vaccine delivery system, supporting previous findings with other yeast species such as Saccharomyces cerevisiae, and highlighting its potential in developing effective mucosal vaccines.