The Efficacy of Anti-Covid Vaccines: How were they Evaluated?

By: Dr. Lim Ju Boo

First written:4.00am 11/07/2021 / Revised: 4.30am 12/07/2021

 

Dear Gentle Readers,

 

Good Morning to you all.

 

Let me start this very early 4.00am conversation by asking ourselves how effective are these anti-Covid vaccines?

 

Let me give just some examples to shorten these discussions.

Pfizer and Biontech claimed “high efficacy and no serious safety concerns through up to six months following the second dose of their vaccines”.

 

The Pfizer-BioNTech also claimed their vaccine was “95% effective”.

A  CDC study reported that a single dose of Pfizer's or Moderna's COVID vaccine was “80% effective in preventing infections”. That number jumped to “90% two weeks after the second dose”, the study on vaccinated health care workers showed.

 

In clinical trials, Moderna's vaccine reported “94.1% effectiveness at preventing COVID-19 in people who received both doses”.

In one Canadian study it was claimed that Pfizer was 87% effective after two doses, Moderna was “72% after one dose”.

 

There was some controversy over the effectiveness of AstraZeneca’s vaccine in late 2020 when it was revealed that some people in the early study groups only received half doses of the vaccine.

 

While AstraZeneca claimed that the vaccine was “70-percent effective”, it was later disclosed that the effectiveness was ”62 percent”. Other sources said that in people who received two full doses, closer to “90 percent in people who received one half and one full dose their vaccines were found effective”.

 

AstraZeneca used these two percentages to average an effectiveness rate at ”76 percent”.

 

Data on Sinovac’s CoronaVac vaccine is limited since a number of  studies on the vaccine are still underway.

 

In one report, investigators report that 97 to 100 percent of people who received the vaccine in clinical trials developed antibodies to COVID-19, but not all of the immune response markers measured in others. Now here is the catch. All these studies use only antibody response to gauge the efficacy of their vaccines as far as we know.

 

With all these claims, I am just wondering how they measure the efficacy of the various Covid vaccines? Did they base their conclusions solely on the antibodies appearing in the blood after vaccination or did they actually measure their results on clinical data on those with and those without getting the infection after vaccination?

 

There is a very huge difference between the two. Antibodies alone not necessary means clinical or protective efficacy

 

To me, to conduct such a study to evaluate the real clinical as well as their preventive efficacy in humans is almost impossible for ethical reasons. Allow me to explain.  

 

There are actually only two ways to evaluate clinical efficacy as far my training and working experience in leading a clinical trial allows me to understand and accept.

 

 

Study Design: 

 

 

Firstly, to briefly mention, we can either use randomized, placebo controlled clinical studies on a large population, or secondly, using matched-control and placebo group for the evaluation in a single blind, but preferably in a double blind study.

 

We will not go into statistical reasons on randomization in the study design. This would be a highly technical subject unless we are trained in medical statistics or in epidemiology, and have been involved in clinical trials as this article is meant only for the general lay reader. But briefly explained, the main reason to prevent bias in the sample selection.   

 

We can also follow up the cohorts longitudinally for many years on those who received, and those who did not receive the vaccination to determine if they confer long-term prevention against the disease.

 

However, briefly described, using either methodology and study design, we need a huge non-infected healthy population and divide them into 3  or even 4 groups.

 

In group 1 we will need to vaccinate all of them with the test vaccine. In group 2 none of them will be vaccinated, and in group 3 and in group 4 they will also not be vaccinated, but they will serve as control groups.

 

In group 3 they will be given a saline injection as a placebo (positive control) instead of the real vaccine, and in group 4 they will be given nothing (negative control). Group 4 may not even be necessary, but may be added if we wish.  

 

The next procedure is going to be a very difficult and highly unethical one. We will proceed to deliberately infect Groups 1 and 2 with the actual live SARS-CoV-2 virus after the vaccination.

  

An independent assessor, normally a senior experienced physician not involved in the study will serve as a “double blind” clinician who has no idea which group was given and which group was not given the vaccine.  

 

He will examine all the individuals in each group, and a bio-statistician will then analyze the data to determine if there is any statistical difference in all the groups. This is the standard way to gauge the clinical and preventive efficacy of any vaccine or any drug or any new treatment.

 

This study design is especially situated for those who already have a disease where we need to test out a new treatment using a drug or a vaccine. It is not meant to test out on healthy individuals.  

 

In other words, it is not normally adopted for testing out vaccines for preventive purposes. But we may have no or little choice if that was our purpose as this gold standard is normally used for those who already have the disease and not those who are otherwise healthy.  

 

 

Indirect Risk Assessment Method: 

 

 

However, there are other indirect methods such as looking at the odds ratio to determine any association between those exposed to a vaccine and any subsequent infection.

 

The use of an indirect method allows researchers to calculate out infection risk by determining the difference between those vaccinated against those not vaccinated. We will not go into the calculation to determine risk assessment  

 

Odd ratios are commonly used in case-control studies or in cross-sectional and long-term longitudinal follow-up cohort studies to gauge the effects of a drug, vaccine or a treatment.

 

But I think the gold standard is still if we can make a direct correlation between those vaccinated against those not vaccinated by directly infecting them.  

 

Unfortunately we are constrained by the highly unacceptable medical and moral ethics involved in deliberately infecting even a single individual, let alone a large population just to test out a vaccine or to carry out a medical experiment. This can never be done.

 

Perhaps we can also look at the epidemiology patterns in a population with and without the vaccines. This would also be an indirect study that can be approached.  

 

So our question now is, did all these studies and claims on the efficacy of the vaccines use human subjects by deliberately infecting them, or were they based on antibodies elicited after the vaccination, or were they assessed indirectly by risk assessment which is more likely?

 

Unfortunately there are lots of reported cases of people getting infected, or reinfected and even died perhaps with antibodies in the blood after completing their 2 doses. How do we explain that then? So we need to look at the antibodies also elicited after vaccination.  

 

Allow me to explain further.

 

The presence of antibodies are entirely different from clinical infection. One is merely the presence of chemical-based immune bodies, the other the presence of the disease

 

 

Antibodies:

 

 

Antibodies are each virus-specific, and they run into millions of classes, sub-classes and sub-sub-classes even though there are five immunoglobulin classes (isotypes) of antibody molecules found in serum, namely IgG, IgM, IgA, IgE, and IgD. 

 

They are distinguished by the type of heavy chain they contain. IgG molecules for instance, some  have heavy chains known as gamma chains; IgMs have mu -chains; IgAs have alpha-chains; IgEs have delta-chains; and IgDs have omega-chains..etc. .

 

Simply put, these variations in heavy chain polypeptides allow each immunoglobulin class to function in a different type and types of immune response or during a different stage of the body’s defense.

 

This means the type of immunoglobulin based on their amino acid sequences confer functional differences for different types of viruses, including the same virus that has mutated into another variant or strain. They are all different. It all depends on the chemical nature of the antigen presentation.

 

 

Vaccine Presentations:

 

  

There are at present different types of vaccines having been produced. Some examples among them are:

 

1.  Inactivated vaccines that are made from dead bacteria or inactivated viruses.

 

2.  Nucleic acid vaccines that use genetic DNA or RNA materials from the bacteria or virus to stimulate an immune response against it. 

 

3. Plasmid DNA and mRNA vaccines that use recombinant  biotechnologies.

 

4. Viral vector-based vaccines that differ from conventional vaccines in that they use the body’s own cells to produce them. This is done by using a modified virus (the vector) to deliver genetic code for antigen such as using COVID-19 spike proteins found on the surface of the virus to introduce them into human cells. 

 

5. Attenuated vaccine created by reducing the virulence of a pathogen, but still keeping it viable. 

 

Hence, the body will respond differently depending on the nature of the antigenic profiles, mainly the proteins expressed.

 

To give some simpler and traditional examples, antibodies against smallpox are different from those for poliomyelitis, that is again different for rabies, rubella or for rotaviral gastroenteritis, and so on.

 

Even flu vaccines differ from season to season due to its changing antigenic variants.

 

Once a virus mutates or changes they will not confer any clinical or protective immunity to a person, and hence all the current vaccines need to be changed.

 

But to develop a vaccine for all is not possible because the immunoglobulin expressed by the body are all going to be different to changing antigenic variants  

 

What we are trying to explain here in simple non-technical language is, we cannot base the efficacy of any vaccine by just measuring the IgM, and IgM response. This is an exceedingly misleading information given to health professionals like doctors, let alone to the ignorant public who has no clue about anything.  

 

Using humans to infect them to test out a vaccine is highly immoral and against medical ethics, so this approach cannot be used.

 

But ideally, this is the only direct method to evaluate, and there is no other better way to the best of my previous experience in conducting clinical trials when I was working at the Institute for Medical Research, Malaysia.

 

This means we need to evaluate their efficacy indirectly through risk assessment of infection pre and post vaccination stages, and I believe this has been done by the vaccine developers.

 

 

Only Humans:

 

 

Unfortunately we cannot use animals to evaluate either, because humans are the only ‘animal’ (zoologically-speaking) that is affected by this virus among an estimated of at least 100  million or more other animals.  

 

None of the other creatures on this Earth has been affected by this virus so far except some of them merely to harbor sufficient of this virus in their bodies as carriers as if like a water dam for adequate supply and distribution for humans like us. After all evolutionary medicine is also my interest and area.   

 

Hence there is no way we can use any other animal models except us to test out the efficacy of these vaccines, and we can only do this indirectly.

 

Now you are free to discuss your ideas further with me.

 

Thank you for reading.

 

 

Jb Lim