Ishtiak Ahmed Chowdhury

One of the most fascinating facts about viruses is that they constantly mutate. The more hosts that a particular virus comes in contact with, the more is the chance of a complex mutation. The viruses don’t really care about obliterating mankind off the face of this planet! In fact, high rates of host mortality would be deleterious for the evolutionary success of any pathogen. All that these particles try to achieve is to hack the genetic mechanisms of a living host to survive, multiply and propagate within the host population so as to ensure their continuation based on rapid and adaptive evolution.

The coronavirus, initially termed as SARS-COV-2 has a region called as the spike (S) protein. The spike protein has two protein subunits, S1 and S2. These two subunits of the spike protein are present on the outer membrane of the virus [2]. The virus has a receptor binding domain (RBD) so that it can attach to a particular receptor on the host cell and insert its own genetic material (RNA) [2]. In fact, this attachment leads to membrane fusion in host cells via “jackknifing motion” of the spike proteins, which requires tremendous amount of energy.

SARS-COV-2 has the receptor binding domain in the S1 subunit of the spike protein that binds to the Angiotensin-Converting Enzyme 2 (ACE2) receptors present on the surface of the cells of various vital organs such as lungs, liver, etc. [2]. However, the body is unable to recognize the spike protein or the viral particles when it is initially under attack primarily due to the lack of appropriate adaptive immune response [2,4]. Moreover, the spike protein is camouflaged by a coat of sugar molecules called Glycans, which protect the spike proteins from being recognized by the body’s immune cells [1].

This is where vaccines play their ultimate role. Most of the mRNA vaccines approved by the FDA train the body’s immune system to recognize the spike protein way before an infection actually occurs and create antibodies to ensure protection from future infection. The spike protein itself is harmless as it is merely a part of the viral anchor that contains no genetic information required for virulent activity or multiplication of the virus [2]. Hence, insertion of the genetic code to create this protein within the host cells and assuring prior recognition of spike protein to avoid future infections are what immunization (mRNA vaccines) tends to achieve [3,4].

Once properly vaccinated as per the recommended number of shots by CDC, the body takes about 2-3 weeks to develop immunity. What this implies is, if the viral particles enter the host after this initial period, the antibodies would be readily able to recognize the spike protein within the host from immunological memory. However, it might require two-three doses of vaccination to attain the appropriate response [3]. Once properly vaccinated, the antibodies would now readily bind to the viral particles so that the antigens can be cleared out by the vigilant immune system.

The delta variant mutation in the spike protein is specifically concerning because the mutation has altered the structure in the Receptor Binding Domain (RBD) of the coronavirus. Hence, the virus is now capable of invading the immune system with more efficiency, resulting in faster and more efficient infection of the host cells (accelerated membrane fusion; rapid entry) [1,2,4].

The silver lining is that the scientific data is extremely promising! The data has vividly shown that FDA approved vaccines are immensely capable of developing immunity against the delta variant [3,4]. In fact, the data strongly suggests that a second dose of immunization from Pfizer or AstraZeneca elicits a strong immune response against the delta variant that can ultimately lead to viral neutralization [3]. Thus, it is of utmost importance that we all get vaccinated not only to develop immunity against alpha, beta or delta but also future variants that could pose significant threat to our survival.

It was not in the too distant past that diseases like Tetanus, Diphtheria, Pertussis, Smallpox and Polio ravaged the globe killing millions of people; many of whom were children. We must not forget how vaccination was the key to literally eradicate some of these maladies off the face of this planet. In fact, lack of vaccination has recently resulted in fresh Polio cases in Ethiopia, Mali, Sierra Leone, Nigeria and Tajikistan [5]. Hence, it is time that we unite and fight against what truly matters because good health is indubitably a fundamental human right.

References

  1. Casalino L, Gaieb Z, Goldsmith JA, Hjorth CK, Dommer AC, Harbison AM, Fogarty CA, Barros EP, Taylor BC, McLellan JS, Fadda E, Amaro RE. Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein. ACS Cent Sci. 2020 Oct 28;6(10):1722-1734. doi: 10.1021/acscentsci.0c01056. Epub 2020 Sep 23. PMID: 33140034

2. Ke Z, Oton J, Qu K, Cortese M, Zila V, McKeane L, Nakane T, Zivanov J, Neufeldt CJ, Cerikan B, Lu JM, Peukes J, Xiong X, Kräusslich HG, Scheres SHW, Bartenschlager R, Briggs JAG. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nature. 2020 Dec;588(7838):498-502. doi: 10.1038/s41586-020-2665-2. Epub 2020 Aug 17. PMID: 32805734

3. Planas, D., Veyer, D., Baidaliuk, A. et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 596, 276–280 (2021). https://doi.org/10.1038/s41586-021-03777-9

4. Olliaro, P., Torreele, E., & Vaillant, M. (2021). Covid-19 vaccine efficacy and effectiveness—the elephant (not) in the room. The Lancet Microbe, 2(7). https://doi.org/10.1016/s2666-5247(21)00069-0

5. Irwin, A. (2020). New polio vaccine poised to get emergency WHO approval. Nature587(7832), 15–16. https://doi.org/10.1038/d41586-020-03045-2