A new vaccine strategy for infectious diseases treatment

Sampriti Roy, University of Calcutta

Since the dawn of a global pandemic this year, infectious diseases have been a popular topic of discussion and research.  With infectious diseases being a threat to the global economy and public health, and with ARBs or antimicrobial resistance bacteria on the rise, the world is in need of progress in the sector of disease management. And fortunately, such is being seen in significant amounts.

One such mark of progress has been made in the sector of nucleic acid vaccine, which offers several unique advantages over traditional vaccines, such as:

1. It is a relatively safer and cheaper approach as it consists of only the DNA or RNA sequence, which is taken up and translated into antigen(s) by host cells.
2. It is highly focused since immune responses are directed toward only the selected antigen(s) of interest.
3. It provides a rapid response platform which capable of producing a protective vaccine in a short time-frame.

However, despite the advantages and DNA vaccinations having been approved for veterinary use, there still lay some limitations that hinder their development from trial to market, such as:

1. Lacking methods to identify the most effective DNA-encoding antigens that can elicit the best immune response;
2. The absence of an appropriate strategy to induce a stable, strong and long-lasting immune response. 

So, in a quest to develop a novel DNA vaccine platform which can deliver potent and long term immune response for infectious diseases, Zhao et al. have reported an efficient multi-epitope self-replication DNA vaccine with a new liposome-polymer hybrid nanoparticles (LNPs) delivery system. 

Noting previous observations where multi-epitope vaccines displayed suboptimal immunogenicity (weaker immune response), the rational design principle followed by the researchers for the multi-epitope DNA vaccine includes:

1.  active B- and T-cell epitopes to enhance immunogenicity;
2.  leader sequence to enhance the stability of mRNA;
3.  Kozak sequence and strong promoter to improve transfection efficiency in mammalian cells; 
4. appropriate linker peptides to improve the immunogenicity;
5. codon optimization to improve expression level.

According to the experimental results, it was found that usage of self-replicating multi-epitope DNA vaccine as a new generation vaccine and LNPs as a new delivery system should be proposed.  Some of the observations found from this study were:

1. Novel LNPs with an mPEG-PLGA core and lecithin shell used in experiments protected the DNA from the degradation of DNase perfectly, released DNA slowly to achieve sustained antigenic stimulation and improved transfection efficiency.
2. Rationally designed DNA vaccine encapsulated in LNPs has potential to stimulate a better humoral and cellular immunity compared to the blank LNPs.
3. Immune efficiency of the multi-epitope DNA vaccine could be further improved by optimization of the NPs (nanoparticles) to reduce the co-administration and sudden release with a suitable adjuvant (boosts vaccine immune response).

Having successfully developed a new DNA vaccine and nano-delivery system, the researchers involved provide a new type of vaccine strategy for the prevention and treatment of several infectious diseases.

Also read: Dirty toilet seats can transmit STDs
Source: https://doi.org/10.1016/j.nano.2020.102338

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