Codon Usage and Adenovirus Fitness: Implications for Vaccine Development

Abstract

Vaccination is the most effective method to date to prevent viral diseases. It intends to mimic a naturally occurring infection while avoiding the disease, exposing our bodies to viral antigens to trigger an immune response that will protect us from future infections. Among different strategies for vaccine development, recombinant vaccines are one of the most efficient ones. Recombinant vaccines use safe viral vectors as vehicles and incorporate a transgenic antigen of the pathogen against which we intend to generate an immune response. These vaccines can be based on replication-deficient viruses or replication-competent viruses. While the most effective strategy involves replication-competent viruses, they must be attenuated to prevent any health hazard while guaranteeing a strong humoral and cellular immune response. Several attenuation strategies for adenoviral-based vaccine development have been contemplated over time. In this paper, we will review them and discuss novel approaches based on the principle that protein synthesis from individual genes can be modulated by codon usage bias manipulation. We will summarize vaccine approaches that consider recoding of viral proteins to produce adenoviral attenuation and recoding of the transgene antigens for both viral attenuation and efficient viral epitope expression.

Transgene codon usage drives viral fitness and therapeutic efficacy in oncolytic adenoviruses

“…This could provide an attractive strategy for vaccine development. In this scenario, optimization of the transgenic antigen would result in attenuation of viral replication together with an increase in epitope expression boosting a specific antigen immune response ( 29 ).…”

Entropy and Fractal Dimension Study of the TDP-43 Protein Low Complexity Domain Sequence in ALS Disease Severity and SARS-CoV-2 Gene Sequences in Virulence Variability

“…A high tendency toward destabilization, which would imply low optimality with the greatest virulence functionality in Orf6, could be interpreted as an apparent paradox [23]. The vaccine design principle based on protein synthesis, with modulation controlled by codon usage bias [24], could be used against the Orf6 and other sequences associated with virulence. The extreme entropy and fractal dimension values observed in the Orf6 sequence could be elucidated in future nucleotide substitution studies that assess cell viability and codon usage bias.…”

Adenoviral Vector-Based Vaccine Platform for COVID-19: Current Status

“…It was found to be effective in mice [ 84 ] and research is ongoing in humans. These replication-competent viral vectors help in improving transgene immunogenicity [ 85 ] and require lower doses to confer persistent immunity [ 86 ].…”