Safety profile of intravenous administration of live Pichia pastoris cells in mice

Abstract Pichia pastoris has been widely used to produce antigenic proteins aimed to integrate subunit vaccines. Moreover, increasing interest in large-scale vaccine production at the lowest cost is rapidly focusing in the development of yeast surface display (YSD) systems for delivery of antigens....

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Bibliographic Details
Published in:FEMS yeast research 2022-05, Vol.22 (1)
Main Authors: Becerril-García, Miguel Á, Flores-Maldonado, Orlando E, González, Gloria M, García-González, Gerardo, Hernández-Bello, Romel, Palma-Nicolás, José P
Format: Article
Language:English
Subjects:
Administration, Intravenous
Animals
Antigens
Hypersensitivity (delayed)
Immune response (cell-mediated)
Immunoglobulin G
Immunoglobulin M
Intravenous administration
Kidneys
Mice
Mice, Inbred BALB C
Pichia - metabolism
Pichia pastoris
Saccharomycetales
Spleen
Splenocytes
Vaccine development
Vaccines
Yeast
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Summary:Abstract Pichia pastoris has been widely used to produce antigenic proteins aimed to integrate subunit vaccines. Moreover, increasing interest in large-scale vaccine production at the lowest cost is rapidly focusing in the development of yeast surface display (YSD) systems for delivery of antigens. In this scenario, the safety of live yeast administration must be warranted, however, such information is very scarce. Here, we assess the intravenous administration (i.v.) of live P. pastoris cells in order to trace dissemination in BALB/c mice and to evaluate the immune response raised against the yeast compared to the well-defined pathogen Candida albicans. Our results demonstrate dissemination of P. pastoris to the heart, kidney, and spleen, but it is quickly eliminated during the first 48 h postinfection (hpi), with persistence in the liver along with mild mononuclear (MN) and polymorphonuclear (PMN) infiltrate, which was resolved at 144 hpi. In vivo delayed-type hypersensitivity test (DTH) or in vitro antigenic stimulation of mice splenocytes demonstrate that transient infection of P. pastoris did not induce a cell-mediated immune response nor increase the level of circulating IgG or IgM. These results demonstrate the innocuous profile of P. pastoris and support its use as a safe delivery system for vaccine development. Intravenous administration of live P. pastoris induces transient colonization in mice, i.e. quickly eliminated without evidence of systemic inflammatory response nor increasing the circulating IgG/IgM levels.
ISSN:1567-1364
1567-1356
1567-1364
DOI:10.1093/femsyr/foac023