Recombinant vaccines in 2022: a perspective from the cell factory

Abstract

The last big outbreaks of Ebola fever in Africa, the thousands of avian influenza outbreaks across Europe, Asia, North America and Africa, the emergence of monkeypox virus in Europe and specially the COVID-19 pandemics have globally stressed the need for efficient, cost-effective vaccines against infectious diseases. Ideally, they should be based on transversal technologies of wide applicability. In this context, and pushed by the above-mentioned epidemiological needs, new and highly sophisticated DNA-or RNA-based vaccination strategies have been recently developed and applied at large-scale. Being very promising and effective, 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 first 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 offered 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: Antigens; Nanoparticles; Nanovaccines; Recombinant proteins; VLPs; Vaccines.

Fig. 1

Principles of antigen engineering and formulation as nanovaccines. A The multimeric presentation of antigens, either as NPs or VLPs, enhances the protective immune response upon administration. B Non relevant NPs or VLPs can be used as scaffolds for the multiple presentation of antigens that are reluctant to oligomerization, either as genetic fusions of chemically coupled upon assembling of the scaffold protein