de Pinho Favaro et al. Microbial Cell Factories (2022) 21:203 https://doi.org/10.1186/s12934-022-01929-8 REVIEW Recombinant vaccines in 2022: a perspective from the cell factory Marianna Teixeira de Pinho Favaro 1,2† , Jan Atienza‑Garriga 1,3,4† , Carlos Martínez‑Torró 1,3,4† , Eloi Parladé 1,3,4† , Esther Vázquez 1,3,4* , José Luis Corchero 3,1,4* , Neus Ferrer‑Miralles 1,3,4* and Antonio Villaverde 1,3,4* Abstract The last big outbreaks of Ebola fever in Africa, the thousands of avian infuenza outbreaks across Europe, Asia, North America and Africa, the emergence of monkeypox virus in Europe and specially the COVID‑19 pandemics have glob‑ ally stressed the need for efcient, cost‑efective vaccines against infectious diseases. Ideally, they should be based on transversal technologies of wide applicability. In this context, and pushed by the above‑mentioned epidemiologi‑ cal needs, new and highly sophisticated DNA‑or RNA‑based vaccination strategies have been recently developed and applied at large‑scale. Being very promising and efective, they still need to be assessed regarding the level of conferred long‑term protection. Despite these fast‑developing approaches, subunit vaccines, based on recombinant proteins obtained by conventional genetic engineering, still show a wide spectrum of interesting potentialities and an important margin for further development. In the 80’s, the frst vaccination attempts with recombinant vaccines consisted in single structural proteins from viral pathogens, administered as soluble plain versions. In contrast, more complex formulations of recombinant antigens with particular geometries are progressively generated and explored in an attempt to mimic the multifaceted set of stimuli ofered to the immune system by replicating pathogens. The diversity of recombinant antimicrobial vaccines and vaccine prototypes is revised here considering the cell factory types, through relevant examples of prototypes under development as well as already approved products. Keywords: Recombinant proteins, Vaccines, Antigens, Nanovaccines, Nanoparticles, VLPs © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Introduction Immune protection against infectious diseases is a main goal in human and animal health [1, 2]. Te current vac- cine narrative is fooded by COVID-19, for which an extremely rapid vaccination response has been impera- tive at global scale. Nowadays, vaccination has not only taken a dominant rule in the scientifc literature but fea- tures of specifc immunization strategies and vaccine- induced immune responses are also fnely dissected and overtly discussed in the media. Tis situation has stressed the challenges posed by emerging viral pandemics and more generically, the transversal needs associated to vac- cine development, irrespective of the involved pathogen- host pair [2, 3]. Te usual failing in incorporating the whole infectious agent in a safe and protective vaccine formulation, either in inactivated or attenuated versions, pushes towards considering recombinant subunit vac- cines [4, 5]. Tis is also supported by the inherent bio- logical risks associated to bottlenecks in the large-scale chemical inactivation of pathogens, either bacterial cells or virus particles [6, 7], or to the potential of reverting to virulence in the case of attenuated strains [7–9]. Also, the Open Access Microbial Cell Factories † Marianna Teixeira de Pinho Favaro, Jan Atienza‑Garriga, Carlos‑Martínez‑Torró and Eloi Parladé contributed equally to this work *Correspondence: Esther.Vazquez@uab.cat; jlcorchero@ciber‑bbn.es; Neus. Ferrer@uab.cat; antonio.villaverde@uab.cat 1 Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallés, 08193 Barcelona, Spain 3 Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, Cerdanyola del Vallès, 08193 Barcelona, Spain Full list of author information is available at the end of the article