Tuesday, April 28, 2020

Coronavirus vaccines enter human trials: An overview of where we stand



Coronavirus vaccines enter human trials: An overview of where we stand

In the race to develop a vaccine against the novel coronavirus there are currently seven frontrunners, all of which have entered human trials. In this report, we take a look at those candidates and give you a brief overview of novel coronavirus vaccine landscape



HIGHLIGHTS 

Seven novel coronavirus vaccine candidates have entered human trials across the world 

In India, six firms are in various stages of pre-clinical vaccine development research 

Experts estimate a novel coronavirus vaccine is around a year-and-a-half away 



In humanity's fight against the novel coronavirus, vaccines have become the Holy Grail. The only way the threat posed by the current pandemic ends is if the human population develops immunity to the novel coronavirus. 


This immunity can either be acquired naturally, for which the virus will have to infect a large chunk of the global population, or be induced with the help of worldwide vaccination programmes.


The first alternative is akin to letting the novel coronavirus run its course and can have devastating consequences. Which is why the second option is our best -- and, perhaps, the only -- bet against the fast-spreading virus. And, there is hope.


The novel coronavirus's remarkable pace is matched by equally rapid advances made in science. It's just been months since the novel coronavirus surfaced in humans, and scientists have already been able to launch projects to identify and develop vaccines to halt the virus's worldwide march.


According to the World Health Organisation's global database of research into the novel coronavirus, there are currently seven vaccine candidates being tried on humans. In this report, we take a look at those prospects (with a special mention for efforts being made in India) and give you a brief overview of the race to develop a novel coronavirus vaccine.


Before we delve in, a word about timelines: Vaccine research is a long process that usually involves at least three phases of clinical, or human, trials. The number of people being given an experimental vaccine increases at every stage with the ultimate goal of testing for safety, side-effects and, of course, the ability to induce immunity. This can take up to a decade.


However, the unprecedented nature of the current crisis has forced scientists to take 'shortcuts' while developing vaccines for the novel coronavirus. What this means is that the timelines mentioned in this article, which are based on the respective researchers' own estimates, are optimistic and must be read with a pinch of salt.


Let's begin.


AD5-NCOV


A joint effort by the Chinese biotech firm CanSino Biologics and an arm of the People's Liberation Army, Ad5-nCoV was the first novel coronavirus vaccine to enter human trials. Ad5-nCoV is currently in Phase II clinical trials and is the farthest along in research for vaccines against the novel coronavirus.


The vaccine uses a harmless virus known as adenovirus to transport DNA of the 'spike proteins' (see image) present on the surface of the novel coronavirus. Once in the body, the DNA present in the vaccine results in the production of these spike proteins.




Most of the novel coronavirus vaccines under development right now target the spikes located on the surface of the virus. The virus uses these spikes, which are made of protein, to latch on to human cells. Vaccines currently being developed hope to disable these spikes and render the novel coronavirus incapable of causing an infection (Getty images)


The idea is that these spike proteins would activate the immune system, getting it to produce pathogen-fighting antibodies that can take on an actual novel coronavirus infection in the future.


Timeline: Phase II trials of the Ad5-nCoV are expected to last six months. Final word on the efficacy of the Ad5-nCoV vaccine and its possible use in the real world is expected to come early next year.


CHADOX1


Developed by British scientists, ChAdOx1 is similar to the Chinese Ad5-nCoV in terms of the technique used to induce immunity. The shot is currently in combined Phase I/II clinical trials that aim to test the vaccine's efficacy and safety.


The Oxford University scientists behind ChAdOx1 are so confident that they have taken the risk of ordering mass production of the vaccine. With the help of several manufacturers -- including the India-based Serum Institute of India -- the researchers plan to produce a million doses by September, doses that will go to waste if clinical trials produce negative results.


Conceptually, ChAdOx1 is similar to the Chinese Ad5-nCoV. The British vaccine uses a harmless virus to introduce genes that produce the novel coronavirus's spike proteins inside the human body. This forces the immune system to build cells that disable the spike proteins -- an ability that would protect against a future novel coronavirus infection.





Timeline: ChAdOx1's full clinical trial is expected to be completed only by May next year. However, the researchers behind the vaccine are hopeful of getting "emergency" usage approval before then, depending on the initial results of their trials. We should know more about ChAdOx1's possible use in the next few months.


INO-4800


Developed by the US biotech firm Inovio Pharmaceuticals, INO-4800 is currently in Phase I clinical trials. INO-4800 has the backing of the Coalition for Epidemic Preparedness Innovations, a global vaccine research coalition founded by the governments of India and Norway, and the Bill and Melinda Gates Foundation, among others.


INO-4800 is based on a relatively new vaccine technique of getting the body's own cells to produce fragments of the novel coronavirus. This is done by 'injecting' DNA into the body. The injected DNA contains the genetic code of, you guessed it, the novel coronavirus's spike proteins. The genetic code, it is hoped, would be read by the body's cells to produce those spike proteins, activating the immune system.


Timeline:According to the company's research listing, Phase I trials of INO-4800 are expected to be fully completed in the first half of 2021.


INACTIVATED CHINESE CANDIDATE


A conventional vaccine that uses a 'dead' version of the novel coronavirus and developed by a state-run Chinese pharma firm reportedly entered Phase II trials end-April. The vaccine is listed on World Health Organisation's database but is relatively unadvertised outside of Chinese media.


According to the state-run news agency Xinhua, the vaccine uses 'inactivated' novel coronavirus cells to induce immunity. Basically, the vaccine is made up of novel coronavirus cells that have been treated in laboratories to ensure no harm to the body. Once in the body, the weakened virus cells would be identified by the immune system, which woud then build antibodies that can destroy the novel coronavirus.


Timeline: According to Chinese media reports, the vaccine is currently in Phase II clinical trials and is on track to enter Phase III. The overall development of the vaccine may take up to a year, according to Xinhua.


PICOVACC


Another Chinese candidate, PiCoVacc is an inactivated vaccine developed by the private biopharma company Sinovac. The vaccine, which is currently in combined Phase I/II trials, aims to generate an immune response by exposing the body to 'inactivated' cells of the novel coronavirus.

Timeline: The vaccine's current stage of trial research is expected to be completed in around four months.


MRNA-1273


Developed by the ten-year-old US biotech firm Moderna, mRNA-1273 is based on a radical -- and so, largely untested -- approach to vaccination that is similar in concept to a DNA vaccine such as the INO-4800.


mRNA-1273 relies on 'information molecules' to deliver instructions to human body cells on how to build a part of the novel coronavirus. These instructions are delivered by molecules known as messenger RNA, or mRNA, which are injected into the human body.


In the case of mRNA-1273, the molecules contain information on building and producing the 'spike proteins' of the novel coronavirus. These spikes, theoretically, would generate a response from the immune system that can protect against a novel coronavirus attack in the future.


mRNA-1273 has the backing of the United State government's National Institutes of Health.


Timeline: Development of mRNA-1273 has been quick, thanks to the new technology on which the vaccine is based. The vaccine is currently in Phase I trials and Moderna has said it expects to begin Phase II trials within a couple of months.


BNT162


Jointly developed by the German company BioNTech and US pharma giant Pfizer, BT162 is a group of four potential vaccines based on the messenger RNA, or mRNA, concept. The vaccines are about to be tested in combined Phase I/II trials in Germany and are likely to enter trials in the United States as well.


The four vaccines use different mRNA technologies developed by BioNTech and more or less aim to get the body's own cells to produce the novel coronavirus's spike proteins. Just like with mRNA-1273, the technology used by these vaccines is radically new and so, remains largely untested.


Timeline: BT162's initial trials are expected to take about a year to complete.


EFFORTS IN INDIA


Indian efforts to develop a vaccine against the novel coronavirus are currently in various stages of pre-clinical research. According to a report by news agency Press Trust of India, at least six Indian firms are engaged in developing a novel coronavirus vaccine, either independently or in partnerships with international companies.


Four of these potential vaccines are currently listed on the World Health Organisation's global candidates list. These include efforts being made by the Ahmedabad-based pharma major Zydus Cadila, Hyderabad-based biopharma firm Biological E Limited and Pune-based vaccine manufacturer Serum Institute of India.


WHEN WILL WE HAVE A NOVEL CORONAVIRUS VACCINE?


We're still in the initial days of vaccine development. Apart from the seven vaccine candidates mentioned above, the WHO has listed over 80 others -- including some by heavyweight pharma companies -- that are in various stages of pre-clinical research.


The novel coronavirus vaccine landscape is fast-changing and is challenging dogmas about clinical trials. Typically, vaccines go through various stages of research, which involve testing on animals and at least three phases of clinical trials, i.e. experiments on humans. All this can take several years, sometimes up to a decade.


But the novel coronavirus's fast spread and impacts on global health and economy have forced scientists to accelerate this process by skipping or combining various phases of research. The approach is fraught with risks but could mean that a vaccine for the novel coronavirus will be developed in record time.


And, what does record time look like?


Experts across the world are of the opinion that at the current pace of research, a vaccine for the novel coronavirus is around a year-and-a-half away. And that is an optimistic assessment. Stay tuned.




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