decade. VLPs can be further improved by encapsulation, chemical conjugation, and

genetic manipulation (Figure 10.1). Bioengineering has been applied to strengthen

their stability and immunostimulatory properties and to generate novel engineered

VLPs, as well as vectors for DNA and drug delivery strategies [4–8].

FIGURE 10.1 Virus-like particles state-of-the-art. VLPs can be classified in non-enveloped

and enveloped structures depending on the nature of the wild-type virus. For both types single or

multilayered protein can be found (adapted from [ 3]). Engineered VLPs: synthetic biology tools

are applied to wide VLP applications. By the addition of chimeric antigens, multimeric vaccines

or pseudotyping of different VLP scaffolds are proposed. Furthermore, surface modification and

cell-specific targeting molecules are also described in the literature for the controlled release of

nucleic acids or drugs, increased immune response, or improved stability of the VLP candidates

(adapted from [ 3, 4, 6]). Production systems: bacteria, yeast, plants, baculovirus-infected insect

cells and mammalian cells are used for the production of different VLP candidates (adapted

from [ 3, 13, 15, 16]). Clinical trials: VLPs are currently tested against several diseases in pre-

clinical studies in several animal models (mouse, rabbit, pig, or rhesus macaque). Currently

there are more than 125 clinical trials (on-going and completed) based on VLPs mainly targeting

cancer and infectious diseases; data obtained from clinicaltrials.gov (Accessed January 2022)

and [ 5, 17]. AAV: adeno-associated virus; AIDS: acquired immunodeficiency syndrome; HPV:

human papilloma virus; MERS: Middle East respiratory syndrome.

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Bioprocessing of Viral Vaccines