Vaccines for Coronavirus What are the Hurdles?
July 01, 2020 | Dr Khurram Mahmood

Vaccines for Coronavirus What are the Hurdles?

Why did we start making vaccines:

Human beings by nature desire control over things, so it was this desire to take control of epidemics that lead humans to develop their first vaccine which was against small pocks vaccine Sara and the dairymaid.

In May 1700s, Edward Jenner, a young physician, he studied his one friend, a gardener's son suffering from the small pocks, Jenner did series of experiments on him and soon the boy recovered. That was the birth of vaccination.

What is the Human Immune System (IS)? Is it a friend or a foe:-

It is just like you are bitten by a mosquito on your arm. And then his bit causes red bump appearing on your skin. 

Ever wondered why? it's due to an immune response to the mosquito's saliva that you may be allergic to.

Your IS is your very own army, intricate and highly organized array of cells and glands to ensure no unwanted guests does any unauthorized activity in our body. Two important cadre of IS are B cells & T cells.

First responders to any act of violation of your body’s sovereignty are macro(big)phages(eater) cells and they do exactly that they engulf any foreign matter present and digest it, following which they send signals to B and T cells to produce antibodies and actively search and destroy foreign invaders respectively. Antibodies are your body’s piece de resistance, smart bombs to be exact that specifically target the foreign invaders known as antigens that they are produced against. B cells remember the invader they were mobilized against this imparts memory and resistance against various diseases. 

Vaccination Strategies:-

In simple words, it is simply a training regimen for your IS to ensure that all resources at its disposal are ready and enabled when called to action stations. This can be achieved in numerous ways, before which I believe it would be appropriate to talk briefly about the types of vaccines that exist. Broadly vaccines are classified as traditional and advanced.

Quick facts about vaccines before we move on

a. Vaccines that work against viruses are directed towards the active component of the virus.

b. The active component of the Coronavirus pathogen is its spike protein.

c. Mutations or (alterations in the RNA of the virus) and their real-time monitoring is vital to developing an effective vaccine.

d. An extensively mutated virus might transform into a benign, angel.

e. We can wait and let our IS figure out how to fight infection without prior training.

However aggressive pathogens may kill you before that happens in the absence of a properly trained IS /vaccination. We shall talk about traditional vaccine types and their pros and cons first.

1. Live Attenuated Vaccines 

Attenuated means making something weak, reducing it in strength, which in a virological context would mean a reduction in virulence. Since the human coronavirus is not a virus that makes chickens sick and it like all its compatriots is an obligate intracellular parasite it modifies itself, adapts and tries to survive. Significant repetition of such attempts to modify itself lead to the complete alteration of the virus, to the extent of the human coronavirus losing its identity. Following which the virus is now ready to be used as a vaccine. Exposure of the human body to such a virus would mount the same response as it would if the body was exposed to a real virus (remember the training simile I used earlier) and the body shall be ready when and if the actual virus comes.

1.   Dead /killed viruses 

A dead virus is not capable of causing an infection however it is structurally similar and can provide adequate training to the body by mounting a response which is synonymous to a response against a fighting fit virus.

       3.   Recombinant Vector for vaccine 

Vectors are portals for transporting things from one organism to another. Frequently employed vectors include, plasmids (Circular molecules of DNA found commonly in bacteria). 

The plasmids being used for developing vaccines against coronavirus are implanted with the genes for the coronavirus spike protein. These suitably modified plasmids are introduced in the system of the individual to be vaccinated, which simulates a mock attack by the virulent virus itself and thus trains the body for the real deal.

  Advanced Vaccines 

 In plain English, advanced vaccines are engineered upon the following central dogma. They use lipid Nanoparticles to deliver the spike proteins to their target tissues or cells. Cell membranes are lipid in nature and thus allow things lipid in nature to pass through them at will. Nanoparticles are tiny balls of lipid that exploit exactly this salient feature of our cell membranes and in effect organ systems.

Clinical trials, why and what for:-

Thousands of pharmaceutical molecules are invented in labs across the world daily. However, only a fraction of them would ever be cleared for human use. Why? It is quite simply because what works in the laboratory doesn't necessarily work on humans. That's where clinical research studies or clinical trials come in. Clinical trials allow us to ascertain how safe and effective experimental drugs are when given to human volunteers. Broadly speaking a drug would pass through three types of clinical studies we call these studies phases.

Phase 1 and phase 2 focus on safety and attempt to establish the maximum tolerable dose without life-threatening side effects. These studies are on a fairly small scale involving a few hundred volunteers. It is only after that the drugs at these stages have shown promising results that Phase 3 trials can begin. Phase 3 trials are conducted on a much larger and in effect broader scale involving thousands of volunteers these large numbers enable us to evaluate the safety and in effect potential effectiveness of the drugs involved more accurately. Every study follows a carefully designed plan called a protocol. This explains the five Ws of the dug being tested. This explains why the study is needed? What the volunteers would have to do? and how their health status would be monitored. Independent review boards referred to as ethics committees must approve these protocols before the studies can begin. They thus have a duty to protect volunteer’s safety and rights. 

Volunteers must also carefully consider the pros and cons before joining a study. They must know, realize and accept that these studies would take time and in effect a commitment to regular visits to their test team which can involve regular invasive testing. The volunteer needs to know that while being part of a clinical trial may grant them a rare insight into information about novel drug things may also go fairly pear-shaped in the form of them experiencing unwanted side effects.

 It is also worth highlighting here that some of the volunteers may not receive any drug at all. They may receive a Placebo. A placebo is something that would look similar to the drug but not contain the active ingredients that produce the desired actions of the drug when introduced in the human body at all. A placebo is a comparator by comparing the test data obtained from volunteers from placebo with an active drug the scientists can determine the drug's risk to benefit ratio and decide whether it should or shouldn't be approved for use in humans.

The ongoing Vaccine race against Corona Virus

Amongst all the candidates in the race to develop a vaccine against the Coronavirus, The mRNA based vaccine by Moderna.Inc Massachusetts has shown the most promising results so far. With the vaccine being developed by Sino-Vac being the second-best contestant. Both these vaccines are representatives of the modern class of vaccines and thus novel drug delivery systems. Each of these vaccine candidates has its strengths and weaknesses. I shall walk you over their pharmaceutical technicalities and pros and cons under individual headings in the simplest possible terms. 

mRNA 1273 Vaccine by Moderna:-

Before I dive right into explaining what the vaccine is, how it works and all its essential details I believe it is worth mentioning here that  

They went from genome to vaccine in 42 days. They have a dedicated team of investors in addition to which they just got a grant of 438million dollars from the US Government.

1. The scientists at Moderna took the gene (a protein or RNA) for the spike protein of the virus from the genome.

2. Used it to develop a messenger RNA, that's where the m in its name comes from.

3. The benefit of developing your vaccine as an mRNA is that as soon as it enters our cells where the vaccine is supposed to be delivered it shall begin making proteins that it stands for. Which in this case shall be spike proteins against which the body shall mount an immune response.

4. The immune response shall come in the form of antibody levels, which can be translated as the number of available troops. These antibodies are referred to as "Neutralizing antibodies" which can be best understood by the following. If a burglar breaks into your house at night tying a string about the end of his nose won't serve any purpose. To prevent the robbery you would have to tie his hands and possibly blindfold him to ensure the robber is incapacitated. Neutralizing antibodies achieve exactly that in a virological context. They bind and block the active site of the virus thus preventing a cellular invasion and in effect an infection.

5. Major obstacles in this regard are the stability of the nanoparticle while carrying a molecule as massive as mRNA for its size and their potential for toxicity. Nanoparticles are like plastic bottles, nonbiodegradable by the body system and thus ay accumulate in the master waste disposal establishment of the human body i.e the liver. For the above reasons biodegradable nanoparticles and nanosheets with mRNA woven in them are also being researched upon.

The Sino-Vac vaccine:-

The Sino-Vac,s vaccine candidate was more thorough in the sense that it has been tested on numerous species infected with the coronavirus. This can be relied upon to cater for all mutations that the virus may undergo. Corona Virus is a continuously evolving virus , fortunately for mankind, the spike proteins still haven't mutated and thus a vaccine can still be developed against the virus. Sino-Vac has tested its vaccine against a wide range of experimental animals from rats all the way to rhesus monkeys.

A critical analysis of various corona vaccine candidates and what can be realistically expected of them

Having bored you with words like Clinical trials, Phases, RNAs and Immunity lets dive right into the key question. When will we have a vaccine? and how long will it be effective for ?To effectively answer this question we would have to analyze each of the vaccines and how they stand the test of scientific scrutiny under individual headings.

Moderna’s Vaccine by Moderna.Inc Massachusetts:-

1. Moderna has released no proper data which can be subjected to scientific scrutiny in any sense of the word what so ever.

2. All that has been offered by the company through its official channels is what's available on the company’s official website.

3. This, unfortunately, is not how we do things in science, a proper and well-structured example of how data associated with a clinical trial should be shared shall be presented later on.

     Salient gaps in Moderna’s version of the story regarding their contribution to the vaccine race are as follows.

a. Moderna states that 4 volunteers out of those who received 25 micrograms of the vaccine dose developed neutralizing antibodies. The question here is WHAT BECAME OF THE REST OF THE VOLUNTEERS?

b. Similarly, they claim that amongst those who received 100 micrograms of the vaccine 4 individuals developed neutralizing antibodies. what we do not know is what the status of these individuals was?

 c. Were they healthy? did they have any comorbids if any? Moderna in its good wisdom has still kept it all to themselves, the reasons for which would be welcome since they would help us find a method to this madness.

d. Moderna claims that the individuals involved in their clinical trial developed antibodies 2 weeks after the second dose, which in itself makes senses your IS takes time to mount an effective immune response. However, they still have left a loophole with a huge question mark attached to it i.e how much time elapsed between the first and the second dose.

Moderna also claims that the individuals who were part of their clinical trial essentially developed two types of antibodies neutralizing and binding. Which would have made more sense had they quantified the levels of those antibodies and laid out who they were and what their health status was.

Having given you a brief overview of Moderna’s "Farrago". Let us 

compare and contrast it with a similar study by Cansino China. This would give us an example of how Men of science should present their work.

1. Unlike Moderna, Cansino gave a complete plan for its clinical trial down to individual weeks and number of days for each phase.<

2. They have clearly stated that 

  (i) their volunteers were between the ages of 18..60.

  (ii)They administered their vaccine via intramuscular injections.

(iii)The first adverse event or adverse drug reaction was seen in 7 days post-vaccination and that the safety was assessed 28 days post-vaccination 

Having meticulously defined the design of their experiment they have then categorically reported the outcome of their vaccination regimen.

3.They state that pain was reported as the most common adverse drug reaction in the middle and low age group within the first 7 days. Which in simple mathematical terms implies that 70 to 80 per cent of those subjected to the vaccine had pain at the site of injection and in effect gives you a choice i.e do you want that pain and the fever that follows or not?. 

4.They have even gone to the extent of defining the frequency of other ADRs i.e fever in 46 per cent, fatigue 47 per cent, headache 42 percent and muscle pain in 18 per cent of the individuals involved in the clinical trial. Lastly, they have delivered a glad tiding through the findings that they have presented Their research publication says and I quote "Humoral response against SARSCOV2 peaked at day 28 post-vaccination in healthy adults and rapid specific T cell responses were noted on day 14 post-vaccination". This is thorough, meticulous and detailed, in plain English it implies that you shall be  at least safe for 28 days. 


Modernas approach to developing a vaccine versus Oxfords approach:-

1. They gentlemen at Astra Zeneca (which is the company collaborating with oxford to develop their vaccine )injected rhesus monkeys and then challenged them with high doses of the virus.

2. They established that the vaccine was successful in preventing pneumonia in monkeys infected with the virus, which is more promising than it appears. I am sure I speak for all of us when I say this that if I do end up contracting this virus I won't like to end up on a ventilator.

3. They convincingly demonstrated that a single dose from their vaccination candidate would be preventive in causing damage to the lungs upon high dose challenge.

4. Their vaccine candidate shows no greater promise than that.

5. As is blatantly obvious from the facts presented above, Astra Zeneca has provided properly cataloged and meticulously documented evidence for every phase and step of the trial whereas modernas vaccine and its details are undocumented and intangible.

It does, however, make one wonder why arent the monkeys developing pneumonia in comparison to their human primate counterparts. Why wasn't a cytokine storm seen in monkeys the way it was in humans.?

CDC, its Lack of professionalism and its contribution as an obstacle to disease control:-

CDCs official website states and quotes "It may be possible that a person can get COVID 19 by touching a surface or objects that have the virus on it ".CDC is the "Holy Grail" for knowledge regarding infections and combating infectious diseases. May be is not the word we would want from a forum as reliable as CDC. Particularly for something as lethal as SARSCoV2.In my humble opinion, CDC is not supposed to think they are supposed to monitor existing data for its validity and report it for knowledge of clinicians and the public alike. There is clear and compelling evidence in research published in reputed journals that virus can survive up to 4 hours on copper surfaces, up to 24 hours on cardboard surfaces,16 hours on polypropylene surfaces, and that the virus has a median half-life of 12.7 hours. It doesn't get any clearer than this does it ?.


I wouldn’t want to leave my readers all in doom and gloom through this article. I have merely presented scientific facts each of which can be defended with tangible scientific evidence.There are rainbow ladies and gentlemen and it's on its way, however, I don’t see it adorning the skies over us any earlier than 2 years. So until then wash your hands, wear your masks and practice social distancing.

Recommended Packages

Dr Khurram Mahmood

Dr Khurram Mahmood pharm.D, M.B.B.S