A ray of hope in the time of Covid-19

On January 10, 2020, a group of concerned scientists in Oxford, UK decided to devote themselves in preparation for a battle to save humanity from a highly intelligent, guileful, and Machiavellian biological enemy, well known now as the virus causing the potentially fatal disease -- Covid-19.

It is nothing but the lowest form of microbial-existence, ruthlessly lethal to the continuity of human life. This narcissistic tiniest poignant human adversary is only visible by an electron microscope, capable of mutating whenever exposed to calamitous entanglement, highly contagious, spreading slowly but with unceremonious resolution, devastating the lives of mankind with particular propensity to destroy the most vulnerable in society. 

The elderly, chronically sick, the immunocompromised, and pregnant women with very little ability to defend themselves against any significant physical and psychological assault are the ones most vulnerable to this shifty but ingenious enemy resolutely taking the maximum advantage of their fragility. 

These scientists have a glorious track record of unflinchingly standing by endangered humanity against any attempt to dismantle and extirpate the very fabric of human life. As recently as 2014, the team had exceptional success with a rapid vaccine invention-response to the Ebola outbreak in West Africa. 

However, on this occasion, they were concentrating on a mammoth task, a significantly greater challenge than anything encountered before -- formulate a vaccine against this virus, potentially more potent than any biological hazard humanity has ever encountered in its last one hundred years of history, since the Spanish Flu wiped out anywhere between 1-3% of the entire world population between 1918-1920. 

Their contest is not mere skirmishes but an all-out war against this unprecedented plague. Additionally, so little is known about its rituals, purpose, or faculties, except that it is ferociously virulent, potentially fatal, and that there is no available treatment and specific method of prevention. 

But the raison d’être could not be clearer -- the hunt for a vaccine against such a mysterious but deadly new virus has to be designed from scratch and progressed to finality at an unprecedented speed while following stringent procedures of invention of a new vaccine, as every moment lost is fought with human fatality. 

It is now clear that the new SARS-CoV-2 virus is extremely efficient at infecting people, and though the viral transmission is relatively slow, once inside human cells, the virus reproduces exceptionally rapidly. The other characteristic that allows the undetected transmission of the virus is the absence of symptoms during the initial phase of rapid growth continuing for a week and over.

The team comprises of and is led by Professor Sarah Gilbert, Professor     Adrian Hill, Professor Andrew Pollard, Professor Teresa Lambe, and Dr Sandy Douglas combining the full strength of two Oxford Groups -- the Oxford Vaccine, and the Oxford Research Group. 

The team started their work designing a vaccine against the virus SARS-Cov-2 responsible for the disease Covid-19 on Friday, January 10. January 10 in my mind is an auspicious date as on that date in 1972, our Father of the Nation arrived back to his people from the jaws of certain death in Pakistan.

The basic structure of the SARS-CoV-2 virus comprises a spherical or circular envelope/wall made of matrix-protein that contains a) a single-stranded RNA, the virus and b) a nucleoprotein. The envelope bears club-shaped glycoprotein projections, the “spike glycoprotein.”

In simpler terms, there is this circular walled virus with club-shaped spike glycoproteins in the wall. The virus arrives at the human cell of the throat and the airways through the mouth, nose, and the eyes and like a space shuttle docks itself on the receptor sites (ACE-2 receptor) of the cells of the throat and airways below as if those cells individually were space stations. 

Normally, the human cells would not allow entry of the virus inside, but once docked on the human cell, the spike glycoprotein works to weaken the cell wall and facilitates the entry of the virus inside our cells. 

Soon, the virus enters our cells and it multiplies exponentially and converts the entire airways and lungs into a massive production factory.

However, the virus does not cause symptoms initially, and later may declare its presence subtly with very mild non-specific symptoms of cough and fever. But the virus continues to be shed continuously through coughing, sneezing, and spitting, infecting other humans.

In some of these patients, it causes massive fluid collection in the tiny units of the lung called “alveoli” and the affected part of the lung develops pneumonia. In others, by heightened uncontrolled response of the human immune system, the virus is capable of mounting an offensive against our very own vital organs: Heart, kidney, brain, etc.

The idea of a vaccine against any microbe is to introduce dead or attenuated/weakened virus/organism into our system that is incapable of producing the full-blown disease but stimulates our immune system to generate significant number of antibodies imparting on our bodily systems the capability of destroying the offending microbes during any subsequent exposure to the virus/organism.

So, the Oxford Group decided to produce a template that would behave physically and functionally similar to Covid-19 but incapable of producing the disease in humans and unable to harm us, at the same time stimulating our immune mechanism to produce enough antibodies to be able to launch an attack on the virus and destroy them during subsequent exposure.

Like the virus itself, their template of the vaccine comprised of two components -- the inner viral component with spike glycoprotein component tagged on the inner core.

The Oxford vaccine termed “ChAdOx1 nCoV-19” is made from a virus, which is a weakened version of a common cold virus (adenovirus), causing infections in chimpanzees. The adenovirus has been genetically changed so that it is impossible for it to grow in humans.

Further genetic material has been added to the adenovirus that makes proteins from the Covid-19 virus, the spike glycoprotein. This protein is usually found on the surface of the SARS-CoV-2 virus and plays an essential role in the virus’s infection pathway by facilitating the virus’s entry into human cells. 

The coronavirus uses its spike protein to bind to specific receptors on human cells to gain entry and cause an infection. So, simply explained, the inner core of the vaccine is a modified virus causing the common cold in chimpanzees. 

It is modified and weakened in such a way that even if it enters the human cell, it is incapable of replicating in humans. The second component of the vaccine is a genetically modified spike glycoprotein capable of initiating and launching a human immune response and generating antibody production but conceptually not capable of any major harm to our body.

The vaccine received approval for trial towards the end of March and phase 1 clinical trial started on April 23 in healthy young volunteers aged between 18-55. Before the clinical trial began, the vaccine was injected into more than 320 people and has been shown to be safe and well tolerated, although they may cause temporary side effects, such as a mild temperature, headache, or sore arms.

The vaccine is already in production. Given the devastation unleashed by the virus, the immediate start of large-scale manufacturing following rigorous safety standard guarantees availability of the high quality, safe vaccine when approved for use.

More than a thousand volunteer participants will be recruited across the UK to complete this prospective, randomized, double-blinded, controlled clinical trial to demonstrate the i) efficacy, ii) safety, and iii) immunogenicity of the vaccine. It aims to assess whether healthy people can be protected from Covid-19 with this new vaccine. 

It will also provide valuable information on safety aspects of the vaccine and its ability to generate good immune responses against the virus. These participants will be randomly allocated to receive either the ChAdOx1 nCoV-19 vaccine or a licensed vaccine already in use against meningitis (MenACWY) that will be used as a “control” for comparison.

The main focus of the study is to find out if this vaccine is going to work against Covid-19, assuming it won’t cause unacceptable side effects, and induces good immune responses. To demonstrate their intended outcome, it would be required for a small number of study participants to develop Covid-19. 

The time required would depend on the levels of virus transmission in the community. If transmission remains high, enough data would be available in a couple of months to see if the vaccine works, but if transmission levels drops, this may take longer, but the trial is expected to be completed at most by September this year.

Professor Sarah Gilbert of the Oxford Vaccine Group is robustly confident of the success of the vaccine and immunization with the new vaccine to begin by September 2020.

Dr Raqibul Mohammad Anwar is a Colonel, Royal Army Medical Corps, UK Armed Forces, and Specialist Surgeon & Global Health Policy and Planning Expert.