Understanding Vaccines

Through anecdotal data and the depleting level at which we are doling out vaccines, it seems that some people are still hesitant to get the vaccine, so we thought we would put together a little explainer, so fears can be assuaged  and the  information can help you make a more informed decision. 

There are 4 classes of vaccines:

1. mRNA, or nucleic acid vaccines: These are the ones developed by Moderna/ Pfizer.  These are done for the first time.  They use genetic material – either RNA or DNA – to provide cells with the instructions to make the antigen. In the case of COVID-19, this is usually the viral spike protein. Once this genetic material gets into human cells, it uses our cells' protein factories to make the antigen that will trigger an immune response. 

Advantages: easy to make, cheap and quick to market. Since the antigen is produced inside our own cells and in large quantities, the immune reaction should be strong. 

Disadvantages: They are experimental so we don’t know their effects 10 years down the line ( but it’s highly unlikely that it can alter DNA.)Also, they need to be kept at ultra-cold temperatures, -70C or lower, which would be challenging for countries like India. 

2. Adenovirus delivering DNA, or viral vector-based vaccines: These are ones developed by AstraZeneca / J &J / Sputnik They do this by using a modified virus  to deliver genetic code for antigen, in the case of COVID-19 spike proteins found on the surface of the virus, into human cells. By infecting cells and instructing them to make large amounts of antigen, which then trigger an immune response, the vaccine mimics what happens during natural infection with certain pathogens - especially viruses. This has the advantage of triggering a strong cellular immune response by T cells as well the production of antibodies by B cells. An example is the vaccine against Ebola.

Advantages: They are well-established technology, so side-effects are known, though it’s more complicated to develop. It’s also known to trigger a B-cell and T-cell response. 

Disadvantages:Scalability, and varied research on when to take the second dose. 

3. Purified protein or subunit protein vaccines: Rather than injecting a whole pathogen to trigger an immune response, subunit vaccines contain purified pieces of it, which have been specially selected for their ability to stimulate immune cells. Because these fragments are incapable of causing disease, subunit vaccines are considered very safe. Examples of this would be Novovax. The successful hepatitis B vaccine licensed in 1986 and recommended for all U.S. babies in their first day of life is a protein subunit vaccine. So is the human papillomavirus vaccines (HPV) that have sent rates of cervical cancer plunging since the first ones were licensed in the 2000s.

Advantages: This is a very robust technology which doesn’t trigger a vaccine response, and very stable with a strong record of safety and effectiveness. 

Disadvantages: Complex to manufacture, therefore it takes time to come to market. Also booster shots are constantly required.

4.Live attenuated virus or Whole Virus Vaccine: Whole virus vaccines use a weakened  or deactivated form of the pathogen that causes a disease to trigger protective immunity to it. This is old, 100 year old technology - invented by Louis Pasteur. This is the method developed by Sinovac, other Chinese companies and Covaxin. There are two types of whole virus vaccines. Live attenuated vaccines use a weakened form of the virus, which can still grow and replicate, but does not cause illness. Inactivated vaccines contain viruses whose genetic material has been destroyed by heat, chemicals or radiation so they cannot infect cells and replicate, but can still trigger an immune response. This is the tech used for measles, Hepatitis A and rabies vaccines. 

Advantages: Robust, tried and tested technology that triggers a good immune response and simple to manufacture.

Disadvantages:  Careful storage necessary and not good for people with compromised immune systems. 

You’d wonder how we managed to come up with a vaccine for Covid-19 in a year, but still haven’t managed one for HIV. HIV is the most heinous virus we have ever encountered, Currently scientists have not been able to come up with a vaccine due to the continuous mutation of HIV in the host body so the body’s immunity is unable to ever catch up. 

On the spectrum of viruses, Coronavirus sits somewhere in between the “one and done” viruses such as polio and smallpox whose mutations are very minor,  and the influenza flu viruses which have so much genetic drift that every year you  need to get a new vaccine (and even then it might not protect you from the various strains). 

Variants:

The bat virus which started in China is not the one that left China. The one that left China and circulated heavily in Europe and America is the mutated D.6.14.G variant. It’s the variant to which all the vaccines are currently made.

The critical question is how much will the virus mutate away from the D.6.14.G to provide protection to the fully immunised populations. Currently, the UK strain and Brazil strain are close enough and proven to provide protection against severe disease, hospitalisation and death.

Every variant should be actively tracked and checked in the lab through an in-vitro assay test. You take serum from an immunised person and see if the B cells can neutralise the variant. This lab data means we won’t have to rely on epidemiology to track and warn us (by which time it’s already too late).

How often would we need to vaccinate?

Measles, Rubella and Polio are one and done viruses that can be eliminated off the face of the earth if everyone is vaccinated once. They stopped circulating in the USA in the early 2000s. The only reason they continue to vaccinate kids for it in the USA is because the viruses still exist in the developing world. Measles is now making a comeback in America because of their anti-vaxxer movement. 

However, Sars-Cov 2 is closer on the spectrum to influenza than these one and dones, and is therefore not an easily eliminate-able virus.

The average incubation period of the Covid-19 infection is 6 days on an average. What you have to aim for in protection either via natural infection or immunisation is the memory of your B-cells & helper T-cells to create the antibody response needed to neutralise the infection in those 6 days. 

The jury is still out on how long this immunological memory lasts,  scientists are hopeful it should be 3-4 years for the vaccine but only once we have the actual timeline data can we know for sure. The reason that they are hopeful especially for mRNA vaccines is that this immunisation causes noticeable lymph nodes enlargement under your arm.  This is a very strong response( also seen in smallpox vaccination) and not common in other vaccines. 

However to believe that we will eliminate this virus absolutely is a fallacy. What we can aim for is slowing its spread and a dramatic drop in the number of infections. But unfortunately, like the ever-changing flu, it will still be circulating. Like the flu, weather has a role to play since its a respiratory virus and hence it comes in 2 waves a year.  We will achieve a slowing down and have it under control when 80% of the population in 193 countries are vaccinated. Till then each country will have  to keep vaccinating its population regularly. 

So, we are going to be vaccinating against this virus for our lifetime. The schedule and frequency of boosters will be finalised as we go along and will know in 2 years or so, assuming no massive mutations take place. What our steady state everyday reality will look like all depends on how much and how quickly 80% population is vaccinated or naturally infected (inclusive of children).

What about vaccine efficacy?

Vaccine efficacy is generally reported as a relative risk reduction (RRR). It uses the relative risk (RR)—ie, the ratio of attack rates with and without a vaccine—which is expressed as 1–RR. Ranking by reported efficacy gives relative risk reductions of 95% for Pfizer, 94% for the Moderna,  67% for the J&J, and 67% for the AstraZeneca–Oxford vaccines. However, RRR should be seen against the background risk of being infected and becoming ill with COVID-19, which varies between populations and over time. Although the RRR considers only participants who could benefit from the vaccine, the absolute risk reduction (ARR), which is the difference between attack rates with and without a vaccine, considers the whole population. ARRs tend to be ignored because they give a much less impressive effect size than RRRs: 1·3% for the AstraZeneca, 1·2% for the Moderna, 1·2% for the J&J, and 0·84% for the Pfizer vaccines.

For more detail on efficacy read this Lancet article:  

Currently comparing trials has been difficult, there were only 168 people in the Pfizer trial but 650 ppl in J & J trial. You pick 8 people per 20,000 available. So the population covered by j&J is much larger and also more susceptible as trials were done across countries and when the virus was peaking in those countries. For the AstraZeneca trial  6 women reported adverse effects in 6 million shots, which is a very small number and statistically irrelevant but the panic created with the announcement made people refuse the vaccine. (Which is otherwise proven to be quite robust.)

What if I wait it out and don't vaccinate?

You may think,  let me take my chances -  I’m healthy, i don’t need to vaccinate, besides my chances of dying from this are low, the chances of dying in a car crash are higher. The reason you should vaccinate is that we don’t know the exact nature of the long term neuro- psychiatric complications seen in 25% of the population, even 6-12 months post a covid infection. The risks of that outweigh the risk from vaccination. It’s a multi-organ inflammatory disease so there will be long term effects for many people especially cardio-vascular similar to Kawasaki disease.

More covid pandemics will come. Three have happened so far in the last 20 yrs. So we need to be better prepared for it. Sars-Covi 1 happened around 2000, Mers happened in 2012, Sars-Covi2 happened in 2020 so in the next 20 years Sars-Covi3 will happen. We need a level of international surveillance that as soon as we know, we get into action mode and are not overwhelmed by it.

So please, find a slot and vaccinate! Mask up, stay safe and wish you health and luck!