Vaccine designers are here to insert death nails into Coronavirus’s coffin

The coronavirus has put the world on tenterhooks and crippled the medical service across the globe. But the time has finally come to bring a sigh of relief; the vaccine designers are here to fire the final fatal shots against the novel coronavirus disease 2019 (Covid-19). Deriving its name from its crown like appearance, Covid-19 belong to the same group of virus as the severe acute respiratory syndrome (SARS) coronavirus (beta Cov lineage B) and the Middle East Respiratory Syndrome (MERS) coronavirus (beta Cov Lineage C). SARS which had its outbreak in China, caused pandemic in 2002 and MERS showed its emergence almost a decade laterwreaked havoc in the Middle-East in 2012. While the first Covid-19 case was detected in China’s Wuhan province around December in 2019, it is presumed that the virus had spread from Wuhan’s sea food market.
Covid-19 and SARS-CoV shares same binding affinity for the host cell receptor- angiotensin converting enzyme-2 (ACE2) and share similar pathogenesis for disease. Covid-19 possesses a large single stranded positive RNA (ssRNA) genome (29.88kb) and it encodes genes for four major structural proteins, where the nucleocapsid (N) is associated with RNA genome and three membrane proteins i.e. the large spike (S) glycoprotein, the integral membrane (M) glycoprotein and the envelope (E) protein. The Spike protein possesses the receptor binding domain (RBD) and is the major subject of interest for the vaccine researchers.
The vaccines can be grouped into eight broad categories – among them the major role players are the activated or weakened whole viruses, genetically engineered proteins and the newest messenger RNA (mRNA) technology- which is acting as formidable backbone for researchers in developing vaccine against Covid-19. Nucleic acid based vaccine like DNA vector vaccine  although found to be safe, stable inside human body and can be rapidly produced but the administration of DNA vaccine by electroporation and possible genome integration is posing a challenge to researchers. On the other hand mRNA vaccines are being successfully used as templates for endogenous protein production inside the body of vaccine recipient and the delivery of mRNA vaccine has been enhanced by the usage of lipid nanoparticles for intramuscular (IM) or intradermal administration.
Moderna, a well-known biotech Company and China’s Cansino Biologics are the forerunner companies to start phase-I clinical trials of vaccine against Covid-19. Moderna’s Covid-19 vaccine is an mRNA vaccine based on mRNA-1273. This mRNA sequence codes the genetic sequence for the spike protein and acts in same manner as the gene therapy i.e. when injected inside patient’s body, causes the host cells to produce the protein and immunises the body against the virus. While both Moderna and Cansino have started their trial on 16th March, 2020, there are dozen more vaccines being developed by companies who are rushing to initiate their trials. A German company CureVac is also working on mRNAbased vaccine against Covid-19. Experimental animals in CureVac’s lab showed a remarkable strong immune response from injection of a single microgram of mRNA. Besides employing new technologies, few researches are still relying on age-old, time-tested technologies. Sinovac Biotech is making its progress in the development of vaccine against Covid-19 by chemically inactivating whole virus particles and simultaneously adding an immune booster called alum. These inactivated virus vaccines are of preference to the researchers as they are age old, tried-and-tested technologies which can be widely used and produced in a large scale across many countries. 
Cansino, a company is trying out another novel approach where they are using a non-replicating version of adenovirus-5 (Ade-5). This approach raised few controversies among vaccine researches, as many people have natural immunity against Ad5 which may prevent the delivery of spike protein gene into human cells and even has a chance to cause adverse reaction in human body. But a press release from the company clearly claimed that their new vaccine has generated “strong immune response in animal models”.
Various other Covid-19 vaccine candidates which are being tried out includes a laboratory version of SARS CoV-2, a replicating but harmless measles vaccine virus that serves as the vector for the Covid-19 spike gene, genetically engineered protein subunits of the virus, a plasmid carrying a gene from the virus and SARS CoV-2 protein that self-assemble into “virus-like particle”. According to many researchers, neutralizing antibodies which play a major role in preventing virus from entering the cells, will assure greater protection against Covid-19. Inovio Pharmaceuticals is on its way to develop a DNA Covid-19 vaccine, is relying on maintaining balance of antibody and T-Cell response, which clear infected cells and has shown a promising response in clinical trials on monkeys.
While several of these approaches are being tried by researchers on a war footing way on laboratory animals and that human trials have already been started, the ultimate goal should be to develop a vaccine which is cost effective, stable, and multivalent as well as provide long-lived immunity against Covid19.

Dr. Aritra Karmakar
Academic Coordinator
Techno India University,WB

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