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.

Mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in mice

“…In addition, genes involved in the origin and spread of novel mutations may further reduce the efficacy of current vaccines and therapies [ 2 ]. Epidemiological data on the survivors of SARS-CoV-2 infection have shown the lack of long-lasting protective antibodies against the virus; further research and alternative solutions are essential to diversify the potential prophylactic methods available [ 3 – 5 ].…”

Recombinant Proteins for Assembling as Nano- and Micro-Scale Materials for Drug Delivery: A Host Comparative Overview

“…In this scenario, recombinant proteins are ideal building blocks, since they are superior to synthetic peptides regarding their flexibility in design and engineering, because the absence of an upper length limit; the capacity to combine functional domains; and their industry-oriented, cost-effective, and scalable biological fabrication. In this context, many types of cell factories have been developed for recombinant protein production [15,[42][43][44][45][46]. Apart from conventional bacterial and yeast species (e.g., Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, and Pichia pastoris), mammalian cell lines, insect cells, baculovirus expression system, and other unconventional and emerging cell platforms can now be found in the catalogue of cell types suited for protein biofabrication [47].…”

“…Under physiological conditions, such an arrangement should render stable cross-molecular interactions and, therefore, derive oligomers with regulatable levels of complexity. Since proteins show mechanical stability and biological activities, protein materials might combine both scaffolding and functional properties, being both fully biocompatible and a smart material [8,15]. Various engineering approaches allow the production of peptides and proteins that can self-assemble under the desired conditions.…”

“…In contrast to synthetic materials, which pose c regarding organic [12], systemic [13], and environmental toxicity [14], the biodeg ity and biocompatibility of proteins as materials make them highly suited for use logical interfaces. The fabrication of protein materials is supported by the capab engineer selected polypeptides that enable either spontaneous or inducible self-as Under physiological conditions, such an arrangement should render stable cross-m lar interactions and, therefore, derive oligomers with regulatable levels of com Since proteins show mechanical stability and biological activities, protein material combine both scaffolding and functional properties, being both fully biocompatib smart material [8,15]. Various engineering approaches allow the production of p and proteins that can self-assemble under the desired conditions.…”

Enhanced recombinant protein capture, purity and yield from crude bacterial cell extracts by N-Lauroylsarcosine-assisted affinity chromatography

“…The large-scale production of recombinant proteins has enabled their exploitation in a wide range of sectors such as biomedicine and biotechnology, for diagnostics, therapy and vaccination [1][2][3][4][5], as well as molecular tools in genetic engineering or catalysts in the biotech industry [3,6]. The production of recombinant proteins, especially at large scale, suffers from important bottlenecks that minimize the yield of functional, usable products [7].…”