The race for anti COVID-19 vaccine

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Nandkumar M Kamat

Speed, efficacy, safety and cost – these are the four factors driving the anti COVID-19 vaccine development. The aim is to make all humans resistant to COVID-19 in the shortest time possible. Obviously, the countries which would get the vaccines in hand first would be free of the pandemic earlier than others. We need an anti COVID-19 vaccine because what we have as anti coronavirus antibodies do not stop the virus from infecting us.

COVID-19 is a different kind of coronavirus. It has four structural proteins, envelope (E), spike (S), membrane (M), and nucleocapsid (N).The S, M, and E proteins account for viral envelopes. The M protein is the most dominant and shapes the envelope. The E protein is the smallest. The S and M proteins are involved in virus assembly during replication. N proteins are found to be associated with the RNA inside the envelope. The most interesting and lethal protein is S protein or Spike glycoprotein. It has S1 and S2 subunits. Spike protein binds to the human ACE2 receptors. These are found in the target cells in the respiratory system. Scientists found that it has a compact ridge. This ridge helps the virus to bind tightly compared to other infectious coronaviruses. Vaccine developers are targeting this protein because it is key to entry of viral RNA into the cell. Because once the spike protein binds with ACE2 the viral envelope fuses with the human cell membrane and infection is initiated.

Four promising candidate vaccines have emerged as the frontrunners. All are claiming success in Phase II trials but these are not sufficient. The real success of any vaccine developer would depend on the most critical Phase III trials. University of Oxford and AstraZeneca in the UK have developed a ‘viral vector’ vaccine based on a genetically modified adenovirus. This is sourced from chimpanzees. It causes cold in these primates because it expresses the coronavirus spike protein. They are testing it in South Africa, the United Kingdom and Brazil.

The second forerunner is from China. In China the race is joined by CanSino Biologics. They used a modified human adenovirus. The third forerunner Pfizer and German company BioNTech are developing RNA-based vaccines using messenger RNA. This mRNA is involved in the synthesis of the receptor-binding domain. The fourth forerunner is US company Moderna in collaboration with the US National Institute of Allergy and Infectious Disease. They are also using a RNA based approach to develop

the vaccine.

With some many viruses and bacteria around us, we have survived because of the antibodies and T cells with long term memory against all previous infections. With COVID-19 – a coronavirus without global vaccination, the present pandemic may wind up within 18-24 months, with vaccination much earlier, say by May 2020.

For the first time in the history of vaccine production we are witnessing a stiff race to produce the effective vaccine using different approaches. Among these the best candidates are the genetically engineered vaccines. But how do we compare the efficacy and safety of different vaccines. The first requirement is development of sufficient quantities of anti COVID-19 antibodies. The second requirement is development of T cells specific to COVID-19. Both CD4 and CD8 T cells need to be detected which can recognise the virus and kill
it.

With the race to develop heating up, so much confusion has been created globally that different people and politicians are giving different timelines for the actual availability of the vaccines. But this is not possible before the Phase I, II and III trial results from the four frontrunners and other vaccine developers close in the race are compared and contrasted with verifiable scientific evidence. The immunological results would be studied by The US government’s Project Warp Speed which is actually aimed to defeat China in the race to develop the first anti COVID-19
vaccine.

There is another initiative from The World Health Organisation (WHO) and the Coalition for Epidemic Preparedness in Oslo. They have funded nine vaccine developers who would compare and contrast their results. In India they are trying Covaxin in at least three stages and if the results are encouraging it may be available within six to ten months. Oxford-AstraZeneca vaccine would be produced by The Serum Institute of India which has plans to make available 300-400 million doses of the vaccine by December. Fifty percent would be used in India. Zydus Cadila Healthcare Ltd has permission to develop ZyCoV-D which they promise to make available after seven months of the trials. India’s Panacea Biotec has planned to produce 500 million doses of vaccine by forming a joint venture firm in Ireland with US-based Refana Inc and they are targeting next year to make it available. Indian Immunologicals has tied up with Australia’s Griffith University to develop anti COVID-19 vaccine. And there are other minor players also who have joined the race.

 For the first time the period that is normally taken for vaccine development has been shortened drastically. There are six stages of vaccine development: exploratory, pre-clinical, clinical development, regulatory review and approval, manufacturing and quality control and none of these can be compromised if the world is to receive a safe and secure, efficient anti COVID-19 vaccine.

In a haste to develop an anti COVID-19 vaccine, these stages
cannot be bypassed or compromised.