Amidst all the enthusiastic talk of developing a Vaccine to fight-off COVID19 (the new coronavirus) and the World Immunization Week (24th-30th April) silently passing by, we at Team ATK felt it’s appropriate to help you gain a basic insight on Vaccines and their utility & limitations in kidney patients.
After all, vaccines form a crucial part of medically preparing all patients of Chronic Kidney Disease for a transplant surgery. Add to that, the fact that SOME vaccines are UNSAFE for transplant recipients, and this topic becomes all the more significant.
So, let’s begin then, shall we?
TABLE OF CONTENTS
WHY DO YOU NEED VACCINES WHEN THERE’S VITAMIN C?!
VACCINE DEVELOPMENT: JOURNEY FROM THE LAB TO THE CLINIC
FACTORS THAT MEDICAL TEAMS CONSIDER BEFORE VACCINATING A KIDNEY PATIENT
CLINICAL CRITERIA FOR VACCINATING KIDNEY TRANSPLANT RECIPIENTS
TABLE OF VACCINES AND THEIR USAGE ON KIDNEY PATIENTS & TRANSPLANT RECIPIENTS
WHAT IS A VACCINE?
A Vaccine is a biological preparation made of “weakened microbes / germs”.
Such microbes /germs undergo artificial tweaking in Vaccine Development Labs in a way that they lose their ability to cause infection but still retain the microscopic features that normally help our immune system identify them before beginning to combat them. This familiarizes our immune system of a “potential enemy” without really causing any true harm.
Hence, vaccines help “train, prepare & strengthen” our immune system to resist an infection from that “specific microbe”, that the vaccine is made of.
So, you must understand that Vaccine is NOT A CURE. Rather, it is a METHOD TO PREVENT INFECTIONS from that specific microbe in future. In a nutshell, Vaccines are the true “immunity-boosters”!
But why do you need Vaccines to boost your immunity when you have Vitamin C?!
We understand your concern. With Multivitamin pills and other “immunity boosting” health products flooding markets, disillusionment is easy. Let us help you understand the importance of vaccines in “boosting our immunity” here.
The “Immune System” of our body is like our personal millitary that fights off any and everything that does not naturally belong within our bodies, whether living or non-living. This ability technically goes by the name, “Immunity”.
But do you really understand what exactly is this Immune System made of?
Here’s the most basic explanation of what comprises your Immune System.
As the poster above explains, the ONLY VALID WAY to truly boost your body’s “Immune Power” against infections is to strengthen your body’s ability to generate an adequate & specific initial response by T-Lymphocytes in the times of need for an Immune Defence.
Does Vitamin C alone help with prompt functioning of T-lymphocytes?
The short answer is, No.
Vitamin A, C & E are anti-oxidants that oversee timely cell renewal & prevent pre-mature aging. They work with lots of blood proteins to carry out repair work in our body. These Vitamins are also critical for a range of body functions such as vision (Vitamin A) & fertility (Vitamin E).
In terms of the immune system, these vitamins help to “repair the borders of our body” in case of any injury. They do so, by collaborating with the necessary surface proteins like Collagen to rapidly heal any micro-scratches, cuts or wounds on our skin, blood vessels and other lining surfaces within the body. This basically prevents foreign bodies, germs, allergens to enter our bloodstream. In addition, since these Vitamins also help in general cell renewal in the body, they “assist in the repair & maintenance” of immunity soldiers.
However, if germs intrude & make their way into the bloodstream, there is no established evidence or mechanism that lets these Vitamins alone enable the T-lymphocytes to identify the microbe & generate a specific immune response to protect us. In such a case, the army of White Blood Cells ends up simply doing Damage Control instead of completely preventing the damage.
This is especially true with certain viruses that don’t even require a cut or scratch in the body surface to enter our systems. They simply attach themselves to proteins on the surface of our mucous membranes (eg: inner lining in nostrils & throat) & “hitch a stealthy ride within”. Talk about being spooky!
How do Vaccines help?
Vaccines, on the other hand, specifically “train, prepare & strengthen” the T-lymphocytes in our blood regarding a potential germ, beforehand.
Each vaccine is specific for the microbe(s) it comprises of. Hence, Vaccines effectively help boost our specific, infection-preventing Immune Power.
Therefore: –
While a generally nutritious diet (and not just mega doses of Vitamin C) is imperative to help keep your “body-borders” secure & immune soldier numbers adequate, Vaccines enable your Immune Forces to “specifically identify & effectively combat” any foreign intruder such that you do not suffer any damage at all.
So, vaccines are crucial to ramp up your immune system against potential infections. Taking Multivitamin pills alone is unlikely to serve the purpose.
CONTINUING WITH VACCINES, WHAT ARE ITS DIFFERENT TYPES?
Based on the “status” of the microbe within a vaccine, it could be of two types:
DO VACCINES ALWAYS INVOLVE NEEDLES?
Mostly, but not always. Vaccines can chiefly be of the following types:
GIVEN BY MOUTH (ORAL VACCINE)
INJECTED VIA EITHER OF THE WAYS AS SHOWN BELOW
Further vaccines can come as a powder that needs to be “re-constituted” with a solution provided with the vaccine kit before administering it. Your nurse has the necessary training to carry out this procedure.
Alternatively, vaccines can come prepared as the more familiar liquid, ready-to-use variant.
THE VACCINE DEVELOPMENT JOURNEY
Before we go into vaccines in the context of kidney patients, here’s a rundown of the rigorous journey any new vaccine undertakes, before it reaches you in the clinic.
Let us first talk about the pre-requisites for developing a vaccine.
INFRASTRUCTURE NECESSARY FOR VACCINE DEVELOPMENT
i. Approved Biotech Research & Development
An appropriate laboratory space with necessary laboratory equipment for uninterrupted daily workflow (microscopes, sterilizers – steam and autoclaves, other research inventory) is of the essence before attempting Vaccine Research.
ii. “Biosafety Cabinets/ Hoods”
You must have seen media-visuals of some scientists working with pipettes, test-tubes, petri-dishes & tiny cylindrical bottles of chemicals kept within a glass chamber. There is only enough space for a person to insert their hands into the chamber. The technical name for such a chamber is a Biological Safety Cabinet or a BSC.
BSCs are sort of like the work-desks of wet-lab researchers and serve two purposes:
They help keep the scientific material within, clean & infection-free
These also prevent spread of any potential infection to the user.
Bio-safety Cabinets can be of different types depending on the level of infectious material that can be safely used for experiments within it.
iii. “Isolated”, expanded & “purified” germ/microbe sample
Next up is the microbe/germ itself that needs to be turned into a vaccine.
To use microbes for research purposes, we cannot simply draw infected blood, urine or nasal discharge and begin our work.
It is imperative, that the germs are “completely separated out” from rest of the material in these infected patient samples (blood, urine, nasal discharge) and grown in clean lab environments before utilizing them for any other biotech applications.
Doing so, “isolates the germs” & helps avoid any cross-reaction or cross-contamination during vaccine development. Usually there are separate biological research companies that provide this service.
It makes the Vaccine much more “specific” than otherwise. The more specific, the better. Else your immune system would stand a chance of ending up “confused” as to what exactly it must be “prepared to fight against”.
iv. Appropriate Genetic engineering tools
These tools are essential for tweaking the microbe on a microscopic level, as medically necessary, before using them for preparing the “draft” vaccine product.
v. Personal Protective Equipment (PPE) Kits
Personal Protective Equipment (PPE) is a must for avoiding any cross-infection or contamination during the laboratory workflow.
A PPE Kit usually consists of overalls, face shields, masks, gloves & eye-protection gear for frontline human resource dealing with the infectious material directly.
INFORMATION REQUIRED BEFORE DEVELOPING VACCINES
i. Complete knowledge of the microscopic structure of the organism
For knowing where to use genetic engineering tools to appropriately tweak the microbe, a clear distinction of the “antigenic” (identity) and “virulent”(infection-causing) segments of the microbe is necessary. It is only then that the infection causing parts of the microbe can be correctly weakened or removed for developing a vaccine.
This part can take anywhere between 2 months to a year depending on how urgent, well-funded & infrastructure-supported, the whole research effort towards developing that vaccine is.
For instance
In case of COVID19 (the new coronavirus) that fast turned into a public health nightmare worldwide, protecting the still unaffected community holds utmost importance. Hence, research efforts worldwide have understandably, been pretty focussed. Academic journals reported the microscopic structure of this coronavirus as early as 2 months from when the first of the cases were reported.
ADEQUATE FUNDING FOR EVERY STEP OF VACCINE DEVELOPMENT
Usually, Academic Research Grants come in from Charities working on a related area, Philanthropic grants and International Research Consortia. The whole pace of vaccine development efforts is entirely dependent on such funding in-flow for the purpose. Right from procuring specific tools and the microbe sample from central agencies to starting clinical trials, seeking regulatory approvals and starting commercial production on a large scale for community use, uninterrupted funding is of the essence.
Once all pre-requisite infrastructure and information is in place, the research lab can begin developing the vaccine. Additionally, the research sponsors start preparing for necessary regulatory approvals when due.
TESTING BEFORE VACCINE LAUNCH – PRECLINICAL & CLINICAL TRIALS
Normally, when there is a public health crisis related to an infection, more than one lab across the world would be vying for developing a Vaccine for the same. These versions produced in the lab are called “Candidate” Vaccines. These serve as a “Rough Draft”.
Such “Candidate” Vaccines go through rigorous testing & trials before some of these can be approved for widespread community use. These are time consuming and expensive. (Think in billions for one vaccine!)
These trials include:
Pre-clinical trials –
i. In the laboratory on human cells
ii. In lab animals like mice to get an idea of how the vaccine reacts in a whole mammal
Clinical trials –
Based on conclusive evidence of the extent of immune protection & it’s safety profile, a segment of these candidate vaccines gets through to Clinical Trials on Humans.
These trials are completely supervised by competent Drug Regulatory Authorities set up by respective Governments. These include:
Centre for Biologics, evaluation & research (CBER) under the FDA in the US
Medicine & Healthcare Products Regulatory Authority (MHRA) in the UK
Drug Controller General of India (DCGI)
and the like.
The sponsors of the Vaccine Candidate follow a multi-step application process that includes:
Application for IND (Investigational New Drug)
Application for Pre-Licensure Vaccine Trials
These applications for Clinical Trials go to a review team which is a mix of a number of stakeholders from various domains. They include but may not be limited to the Project manager, Medical Officer, Statistician, Pharmacologist, Pharma-kineticist, Chemist & a Microbiologist.
Once approved, the Vaccine Candidate undergoes a rigorous testing under multi-phase Clinical Trials as below:
REGULATORY APPROVALS FOR MARKET LAUNCH
Upon completion of Clinical Trials, the Vaccine research sponsors need to file a separate set of applications with competent local regulatory body. This is for Scrutiny & Approval of the new Vaccine for large scale production for community use.
These require the following:
Biologics License Application
Inspection of manufacturing facility
Presentation of findings of the Clinical Trials to the Advisory committee of the competent local Drug-Regulatory Body.
In case of USFDA, findings are presented before the Vaccines & Related Biological Products Advisory Committee (VRBPAC).
Regulatory Approvals for commercial manufacture of Vaccine Products are subject to:
If the vaccines are proven to be safe & effective
Its Benefits outweigh risks
If a valid manufacturing facility with appropriate health & safety standards
MARKET LAUNCH FOR COMMUNITY USE & FEEDBACK
Once the Vaccine Product matures through all the above stages of Regulatory approval and goes into the market, the respective regulatory bodies keep track of the vaccine’s “clinical performance”. This is to monitor, collect & analyse information related to Side-effects of the Vaccine Product in the larger community. If warranted, a vaccine product could also be “recalled”.
The US FDA allows all concerned segments ranging from Patients, Parents, Healthcare providers, pharmacists and Vaccine manufacturers to report side-effects under due procedure.
So, that is about the journey of your Vaccine from the lab to the clinic.
Only 1 out of 10 Vaccine Candidates are able to complete all the above phases of trials to be approved for use in the clinic!
Unless there is an unprecedented emergency like the COVID-19 crisis right now, the average time to bring in each Vaccine Product to the market ranges from minimum 5-7 years.
You see, just how rigorous, resource-heavy, capital-intensive, time-consuming and strictly monitored, the entire process of Research and Market Launch of just ONE vaccine is. And that’s because public health is serious business and rightly so.
Armed with all this knowledge, let us delve into the topic of Vaccination in Kidney Patients and transplant recipients. Click on the image below to go to the article.
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