CORONA MENACE: THE ERA OF GENETIC ENGINEERING – THE NEXT GENERATION OF VACCINES FOR CORONA VIRUS

Pfizer vs Astra-Zeneca

“Although COVID continues to be the menace but real culprit is the declining vitality of human immune system”

By Prof Kuldip Sidhu

(Part II)

ASTRA-ZENECA VACCINE

The company used the chimpanzee’s adenovirus that has been engineered to become non-replicating (non-infectious) in human as a vehicle to deliver corona virus spike protein (S) DNA. The latter was extracted and amplified in the lab before inserting into the adenovirus DNA. This recombinant adenovirus is used as vaccine directly. Once injected, the recombinant adenovirus DNA is picked up in the cell cytoplasm as a droplet and delivered to the nucleus (Figure 2 top part) and the company  claims that DNA does not integrate with the host DNA but instead uses host enzymes to form mRNA. Our cells constantly produce (transcribe) messenger(m)RNA and synthesize (translate) protein,  since after vaccination, our DNA now contains also a part of corona virus spike protein DNA, many copies of spike proteins (S) are also produced and expressed on cell surface.  These new spike proteins on our cell surface are identified as foreign by our immune system and consequently it produces anti-bodies against them and attack the spike proteins on corona virus, killing the virus. If our immune system is robust enough, it can fight corona virus by itself producing antibodies against spike proteins by natural immunity by virtue of our defence  army, T-cells and C-cells (Figure 2 left side).An added advantage of such DNA vaccine is that it can be stored at 2-8̊ C temperature because DNA are generally very stable. Since Astra-Zeneca is using host(human)biosynthetic machinery for producing spike proteins and anti-bodies, it is more specific and efficacious (approx. 70%) including against Delta strain. But why it causes some blood clots in younger population, is not clear or is it because it is genetically engineered? Their clinical data are based on studies with 12, 000 volunteers, that included both the treatment group and placebo(control) and they were followed for about 120 days after vaccination. Long term followup, however, may reveal further the safety profile of this vaccine.

PFIZER-MODERNA VACCINE

Unlike Astra-Zeneca, Pfizer-Moderna vaccine does not use any genetically engineered virus as a delivery mechanism, instead it uses artificial lipid sphere to deliver spike protein mRNA. First the spike protein DNA is isolated from virus and amplified (scale up) by inserting into the DNA of a familiar  E-coli bacteria by recombinant technology (your genetic material functioning in bacteria – pretty amazing*) and the corresponding scaled up mRNAs are collecterd. Normally mRNA are very short lived in our cells and are protected by being present or enclosed in special proteins called riboneuclear proteins(RNP-ribosome). Threfore, Pfizer first protected all of the spike protein mRNA by inserting these into lipid spheres (Figure 2 right side). The latter are used as vaccine and once injected are taken up by human cells and used directly for translating into spike proteins by ribosomes. These spike protein then also expressed on cell surface that evoke immune response and virus particles are killed like in Astra-Zeneca vaccine. The only difference is that Pfizer vaccine uses mRNA, it has to be stored frozen (-70 ̊C) as mRNAs are very unstable. The vaccine per se is very efficacious-effective (approx. 95%) and efficient as it involves only translatingthe mRNA to protein directly in the cytoplasm of the cell.These data are based on large group of 43, 000 volunteers including placebo control in this study. Relatively safe apart from acute reactogenicity at the site of injection but some recent concernby the European Medicine Agency (EMA) said that it has established a possible connection between the mRNA COVID-19 vaccines of Pfizer and Moderna and rare heart inflammatory conditions like myocarditis and pericarditis. Incidence is very rare, 300 cases so far mostly in young out of 200 million doses delivered. Symptoms are mild and patients recovered.

Viruses and bacteria including other pathogens are part of  human evolution, and have been in coexistence with human race and in close association for ages (gut bateria for example), simplex (shingal) viruses, other retro viruses (our DNA contains about 8% of viral DNA) and some of microbes have become part of our body (mitochondia in our cells were once bacterial infection; even nucleus in the cell is considered to be of viral origin).The sycytial (multiple cells coming together as a sheet as in placenta) protein also derived from virus helped human to adopt sexual reproduction as an evolutionary advantage and is responsible for placenta (sheet of cells) formation. Therefore,I suppose all this is a part of  evolutionary step making us  more resilient species for the future.  So everything hapening around us now may not necessarily be all bad for us – a path for deveoping human race to intergalactic species!

Both these vaccines and some others similar in offing are using cutting edge genetic engineering technology for the first time and though seem working to contain corona virus but their long term affects need to be assessed.Similarly appearance of acute and chronic cases of post COVID infection known as long COVID haulers (about 30%), continue to suffer even after COVID recovery, these cases need to be assessed more critically so as to combat the onset of long term morbidity with this disease. My research group is looking into it.The need of the time is to get majority of the population vaccinated so as to attain the ‘herd immunity’. It is not only the science and health issue but is also the logistic and policy issue for nations to be coherent and save humanity. Science can do wonders and it’s always enticing  to my heart and to learn more!

*Ananda Mohan Chakrabarty (4 April 1938 – 10 Jul 2020) was an Indian American microbiologist, who pioneered recombinant technology and had a great struggle in protecting his technology whereby he could engineer  bacteria so that it could convert oil into water. The idea was to clean up oil spillage in seas caused by major ship disasters. The key argument against his discovery was that what if the genetically engineered bacteria escapes into the Persian Gulf! However, he was eventually granted the patent with a stringent oversight.

A CHINESE scientist, Jiankui in 2018 claims to have created the world’s first “genetically edited” babies by CRISPR technology. The twin girl’s embryos were edited in the womb that have now altered DNA, protecting them against HIV, the AIDS virus. But use of the gene-editing procedure has been branded “monstrous” by critics and is banned in embryo now, however, adult cells editing as in some cancers allowed.

FIGURE 2: Natural vs Acquired immunity (vaccination) (adapted from webpage)