directly injected into dendritic cells that can present the antigen to the adaptive

immune system. Alternatively, an indirect route can be used, injecting the vaccine

into the muscles or the keratinocytes, which will produce the protein. Antigen-

presenting cells take up peptides or protein fragments released from muscle cells

and present them to the adaptive immune system.

A major concern for using DNA as the immunogen is the possibility of chro-

mosomal integration and consequently perturbation of the genome. However,

careful evaluation of several veterinary DNA vaccines have not provided any

evidence of genomic integration of the exogenous DNA [14]. Another cause for

unease relates to the fact that autoimmunity is linked to the presence of antibodies

against DNA and raises the possibility that administration of exogenous DNA could

elicit an antibody response and hence generate or exacerbate autoimmunity.

However, contrary to expectation, clinical trials with patients suffering from dia-

betes [15] and multiple sclerosis [16] were reassuring.

A big advantage of using genetic material as an immunogen is that the bioma-

nufacturing process is a lot easier than that for proteins, given that all DNA mo-

lecules share similar physicochemical properties and therefore production does not

have to be tailored to each vaccine. From the identification of the sequence to

production of the DNA vaccine is a relatively rapid process in comparison to the

production of a protein-based vaccine, which can involve purifying a protein sub-

unit from a pathogen or producing recombinant protein to serve as the antigen.

Despite these advantages, trials with DNA vaccines have not been very successful

at eliciting a robust immune response and several approaches are being investigated

to increase their immunogenicity. These include improvements in the design of the

vector and the use of adjuvants [17].

3.4.6

RNA VACCINE

Similarly, instead of DNA, it is possible to use RNA. In fact, in theory, RNA vaccines

have a distinct advantage in that RNA molecules need to be delivered just to the

cytoplasm, avoiding the additional step of transport to the nucleus and there is no fear

of genomic integration, as is the case with DNA. However, in practice, RNA vaccines

were not favored for development due to the concerns of instability and their higher

inflammatory potential as a result of recognition by several endosomal TLRs (TLR 3,

7 and 8) and cytoplasmic RNA sensors (RIG-1 and MDA5) [18]. Although efforts

have been under way to address these concerns for several years, they came together

in 2020 in the form of highly effective mRNA vaccines in the face of the SARS-CoV-

2 pandemic. The identification of new nucleosides that could enhance stability, better

understanding of the RNA-sensing mechanisms to control the inflammatory response

and the development of lipid nanoparticles (LNP) as safe and effective delivery

agents, have all contributed to this success [19].

3.5

CONCLUSION

Although we have learned a lot since the early attempts of vaccination against small

pox over a 1,000 years ago, the search for strategies to increase immunogenicity

Introduction to basic immunology

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