COVID-19 Vaccines: Types and Mechanisms of Action

Viruses use their spikes to attach themselves to human cells during an infection. It exploits the machinery of the host cell to replicate after entering the cell, creating viral proteins and genetic material. As the host cell dies, they are combined into new virus particles and discharged.

Resultantly, more cells are infected by new virus particles, which destroy body tissues and cause symptoms. Infected cells send out warning signals to the immune system by exhibiting viral protein fragments on their surfaces. By doing so, infected cells are believed to transmit the viral antigen to specific immune cells, such as cytotoxic T-cells, and so activate them. 

At the same time, detritus from dead cells and virus particles are taken up by so-called professional Antigen-Presenting Cells, the most effective of which are dendritic cells.

Dendritic cells patrol the tissues of the body, constantly sampling their surroundings for intruders. Dendritic cells swiftly leave the tissue after capturing the antigen and travel to the next lymph node, where they present the antigen to another type of immune cell known as helper T-cells. B-cells in lymph nodes are also activated by viral particles. 

These immune cell clusters collaborate to mount two types of antiviral immunity: 

1. Cell-mediated immunity 
2. Antibody-mediated immunity 

However, the procedure could take many weeks, during which time the person will be sick and the virus will have damaged a large number of cells.

Vaccines give viral antigens to the immune system without inducing disease. A vaccine-generated immune response is comparable to that induced by a natural infection, albeit some vaccinations may only induce antibody-mediated immunity, making them less effective. Even when there is no infection, the immune system can produce symptoms that resemble a mild infection. For a few days, the lymph nodes near the injection site may become swollen and sore as they begin to produce antibodies. This is proof that the vaccine is working against infection.

Many existing vaccinations contain a virus that has been attenuated or inactivated. Because the entire virus is used in these vaccines, significant safety testing is required. In those with weakened immune systems, attenuated vaccinations may still cause sickness. 

• Only antibody-mediated immunity is induced by inactivated vaccines (Sinovac, Covaxin). 
• Only a portion of the virus, usually a spike protein, is contained in subunit vaccinations (EpiVacCorona). 

Although these vaccinations do not cause disease, they may not be seen as a danger by the immune system and hence fail to elicit the desired immunological response.

As a result, adjuvants are frequently used to encourage antigen-presenting cells to recognize the vaccine. A subunit vaccination could alternatively be made out of empty viral shells that haven't been genetically modified. These vaccines may not require adjuvants to be seen as dangerous because they have the size and structure of a disease, but they are difficult to make.

Instead of the antigen itself, nucleic acid vaccinations contain genetic instructions for generating the viral antigen. Viral DNA is introduced into the nucleus of the cell, where it is translated into mRNA. In the cytoplasm, mRNA is translated into viral spike protein. Like other types of vaccines, the protein is then exhibited on the cell surface.

To reach the cell's nucleus, naked DNA vaccines (Inovio) require a specific delivery technique. Alternatively, a virus that isn't related to the DNA could be utilised to distribute it. The vaccine is also known as a viral-vector vaccine (Sputnik V; Johnson & Johnson's) in this situation. 

The Oxford-AstraZeneca Covid-19 vaccine, for example, uses a chimpanzee's adenovirus as a vector. The coronavirus spike gene is inserted to the adenoviral genome, which has been edited to eliminate viral genes. The viral vector cannot reproduce or cause disease in this manner, but it does serve as a vehicle for delivering the DNA. Because most people have been exposed to human adenovirus and have developed immunity to it, a non-human adenovirus is employed. Immunity may kill the vehicle before the DNA can be delivered, reducing the vaccine's effectiveness.

Concerns about viral DNA integration into the human genome have arisen as a result of DNA vaccinations. However, research in animal models have revealed that the incidence of integration is far lower than that of natural, spontaneous gene changes. 

mRNA vaccines (Pfizer, Moderna) deliver mRNA, which provides the instructions for producing the viral protein. mRNA molecules are transported in a lipid coating that will merge with the cell membrane when it reaches it. The mRNA is translated into viral antigen in the cytoplasm and subsequently presented on the cell surface. mRNA vaccines, unlike DNA vaccinations, are highly unlikely to incorporate into the human genome.  

Apart from all of the information we have so far, we are unable to compare any vaccine to another at this time. Because there is still a lot of research to be done on this subject.

VACCINE EFFICACY AND COVID MUTATION

Scientists were concerned early in the epidemic, fearing that the coronavirus may evolve into something more deadly. Unfortunately, that worry was verified in November 2020 when the first "variant of concern" was found. The newly identified variation, also known as COVID-19 - B117, has been linked to a large increase in cases particularly in London and south-east England and many other parts of the world. 

So, in this blog, I’ll be talking about COVID Mutations and what it means for us. So, Let’s begin by taking a brief look at mutations and how they occur.

In biology, a mutation is something that causes a change in the genetic material. Each and every element of a cell's existence is controlled by the same genetic material. A cell's genetic makeup determines how it develops, functions, behaves, responds, and finally dies. These mutations can occur for a variety of causes. It can occur as a result of errors, radiation damage, or chemical exposure.

In fact, mutations can happen at any time. As a result, mutations might be harmful, neutral, or even beneficial to an organism.

So, you might be wondering how Coronavirus is affected by mutation?

Well, the coronavirus attaches to our body's cells using a specific protein. Spike proteins are proteins that aid the COVID virus in latching onto human cells and initiating infection. Because of mutations in these proteins, the virus is able to adhere to our cells more firmly, making it more infectious. 

Furthermore, mutations in this area allow the virus to avoid our body's own immune system, allowing it to spread unchecked. This mutation has been termed as ‘E484K,' and as of December 1, 2021, the UK recorded a total of 14000 instances each day, with a decreasing trend. 

After this strain on 5th Jan 2021 – UK was reporting a record high 60000 cases per day with an increasing trend. It has been discovered that the new strain is more infectious than the previous ones. According to the CDC. "Multiple lines of evidence show that B.1.1.7 is more effectively spread than other SARS-CoV-2 variants". According to UK Biobank researchers, most patients infected with COVID-19 maintain the antibodies for three to six months.

Your antibodies may not be able to protect you if you come into touch with another strain of the virus, such as the extremely infectious variety from the United Kingdom, and physicians feel your risk of reinfection is considerable. This is concerning because it raises the risk of coronavirus reinfection, especially in severely or chronically sick individuals.

What does this mean for us in the present? 

Things appear to be on the mend for the time being. The need of fast and decisive action appears to have been recognised across the world. Countries shut off overseas travel as soon as the news of the new strain became public, particularly from the United Kingdom. Those who had already returned were tracked down, quarantined, and tested as soon as possible.  Even nations like India, where covid has already impacted over 10 million people, have successfully halted the spread of this alien strain.

What about the vaccine? 

Well, things are a little strange here. Studies were conducted in New York, Texas, and Cambridge to determine the efficacy of current vaccination alternatives against the new strain. They evaluated freshly vaccinated people' antibodies against the novel covid 19 UK strain. Their findings revealed that, while the vaccine's efficacy in protecting against versions harbouring the E484K mutation was somewhat decreased for some persons, it was still within acceptable limits for the majority of people. It's worth noting, however, that the research mentioned above are based on relatively tiny sample sizes, so any conclusions drawn aren't conclusive.

What does this mean for the future? 

This mutation is a foretaste of what's to come. Covid's future will be filled with fresh shocks and unknowns. The long-term effects of this epidemic are yet unknown. It's possible that another altered strain isn't far behind. On a more optimistic note, all hope is not gone; we have fresh information and experience with which to prepare.

We have global mass vaccination programmes that are coordinated by corporations all around the world and sponsored by governments, and they have the ability to permanently address this problem. To reduce the load, we're looking into medicines, novel therapies, and complementary and alternative medicine. Governments are actively taking efforts to eradicate this illness, such as mass media campaigns, raising public awareness, boosting health spending, and working with scientific specialists.

The Delta Variant: Everything You Need to Know..!

Are you ready for some COVID news? Yeah, I know, me neither. But I wanted to talk about something that’s been in the news, and that you may even have questions about: the Delta variant. 

So in this post, we’re going to talk about what it is, why it’s here, and what you need to know.

The Delta variant is a strain of the SARS-CoV-2 virus, which is the virus that causes COVID-19. It’s one of several variants that’s acting unique enough to qualify as a distinct strain. Those get Greek letters for names right now, like Beta and Gamma, plus the first dominant strain: Alpha.

Since it was identified in late 2020, it’s quickly becoming the dominant strain in many parts of the world. That includes countries that had successfully managed earlier strains and relaxed public health measures, like the United States and France. And what makes this variant worrisome is that it looks like it’s more easily transmissible than previously dominant strains. 

The World Health Organization (WHO) says that the Delta variant is the most transmissible of the variants identified so far. We don’t yet know why it’s able to spread so much more readily, though.

One study has proposed that it’s because infected people have higher viral loads, that is, more copies of the virus in their bodies. If true, that would mean that the Delta variant reproduces faster and is more infectious at early stages than other dominant variants. This variant may also affect our bodies differently than previous dominant versions of the virus. 

The study I mentioned also suggested high viral loads may be related to a shorter incubation time, meaning infected people show symptoms faster. However, this paper has not yet been published or passed through peer review, so we’ll need further confirmation. 

Other data indicates that the Delta variant’s symptoms might be slightly different, with headaches, fever, sore throat, and runny nose being common while cough and loss of sense of smell aren’t. It also comes with some new symptoms, including hearing loss.

But are those infections more severe?

Well we’re not sure yet..!

Some experts say that may be likely, and there are some reports that the Delta variant may be more likely to lead to severe illness compared to other strains. And a report from Scotland suggests hospitalization for unvaccinated individuals is twice as likely if the patient is infected with the Delta instead of Alpha variant. It might be that the Delta variant is more dangerous. Or that it’s spreading faster through more vulnerable populations. And easing up of public health measures has certainly played a role as well.

The situation in India seems to have been a perfect storm. Their vaccination campaign was just starting to get going. Officials had relaxed restrictions on large public gatherings, and that plus the heightened transmissibility may have let the Delta variant spread through the population rapidly. 

But it’s not a simple matter of India relaxing social distancing and other public health measures. Because here’s where we run into another wrinkle: In Australia, most of their public health measures, like contact tracing and social distancing, have been seen as a model worldwide. And the Delta variant has punched right through them. Relatively speaking, anyway. 

For most of 2021, Australia has managed under 100 new cases a week, but since July, that number has skyrocketed to around 2000 a week. That’s still low compared to some countries, but it’s pretty troubling. What Australia hasn’t had, so far, is a high vaccination rate. But even vaccinated individuals may need to be wary.

There’s been a lot of attention paid to so-called breakthrough infections, which is where someone who has been fully vaccinated still gets sick. There have been a few well-documented outbreaks that included a substantial number of vaccinated people. Now, it’s worth noting that some breakthrough cases are expected. No vaccine is ever perfectly effective at preventing infection. It’s worth the reminder that most of the vaccines in use right now were first tested around their ability to prevent severe disease, not necessarily stop transmission.

Data from the World Health Organization suggests that a number of vaccines, including Moderna, AstraZeneca, and SinoVac, have so far been over 80% effective against severe disease, hospitalization, and death. 

So the question becomes whether the Delta variant is more likely than others to infect vaccinated people. And whether those people would go on to spread it. We didn’t have much data concerning vaccines and the Delta variant, but we have some. 

A paper published in July in the New England Journal of Medicine suggested that two doses of both AstraZeneca and BioNTech-Pfizer’s vaccines are effective against the Delta variant. They lost only a few percentage points of efficacy compared to an older strain. Now, both of those vaccines are administered in two doses. And the paper did find that only a single dose of either was less effective against the Delta variant, dropping from about 50% to only about 30%. That seems to be the case for other variants as well. Altogether, it is possible for someone who is fully vaccinated to be infected with any variant. 

According to the CDC and some pre-print data, people with breakthrough infections of the Delta variant may have a viral load just as high as someone who isn’t vaccinated. And remember, the Delta variant might come with a lot. This has raised concerns about how much vaccinated people might still spread the infection. Though it’s worth noting that high viral load isn’t necessarily an indication of heightened infectiousness. It could be that those viral particles are present in the body, but have been deactivated by the immune system. So they’re not actually a problem. And as more people get vaccinated, the proportion of breakthrough cases to normal cases will rise, because the proportion of vaccinated people to unvaccinated people will rise, and you can’t have a breakthrough case unless you’re vaccinated. That’s what it is.

So, what can we do?

Well, we don’t yet have a lot of concrete answers regarding the Delta variant. But remember that vaccines still seem to work. And by “work”, here, I mean they help limit severe illness, hospitalization, and death even if people do get sick. 

Some of the vaccine manufacturers are looking into booster shots, but many public health experts say they would rather focus on getting to people who haven’t yet had an opportunity to get even a first dose. And this isn't just a question of logistics, but equity, as most of the available vaccines have gone to rich countries so far, leaving many vulnerable populations waiting. 

We still do have all the stuff we had at the start of the pandemic. I’m talking about you’re quarantining if you’re feeling sick, you’re washing your hands, all that good stuff. These will continue to be an important part of limiting spread as much as possible. We can see from Australia’s example that social safety interventions like distancing aren’t bulletproof. But vaccines, in the absence of those same measures, aren’t enough either, because breakthrough infections happen, and a lot of people remain unvaccinated. It’s going to take a comprehensive strategy to stay ahead of this thing. 

Meanwhile, experts are keeping an eye on this and other variants, like Lambda, which also appears to be more infectious and possibly resistant to vaccines. Unfortunately, even though we all really, really would love to believe otherwise, COVID isn’t over yet.

Thanks for reading this post. 

I hope it brought a little clarity to the confusing ongoing situation we find ourselves living in...!

STAY SAFE AND FOLLOW PRECAUTIONS..!

Vaccine Side Effects are Actually a Good Sign...!

Developing a vaccine is not an easy task as it involves a number of steps. Image below is showing the common steps involved in the process of developing a vaccine: from development in the lab, testing, approval, manufacturing and all the way to getting it to millions of people.

But arguably the most important part is here: is the human trials. Where the vaccine is tested on real people, in three main phases, starting with just a small group of people, and ultimately testing a group of thousands. This is where scientists confirm the effectiveness and safety of the vaccine on a large scale. Before that, scientists scrutinize its effectiveness. But before any of that, a vaccine has to pass this crucial first phase, where scientists study the side effects.

Dr. Kirsten Lyke (University of Maryland, School of Medicine) led a Phase I trial for the Covid-19 vaccine made by Pfizer and BioNTech. She says: ''Side effects are a possibility with any vaccine. In general, it's nothing to fear. It's our own immune systems kicking in and doing what it's supposed to do''.

The most common flu vaccine this year, for example, comes with a chance for many normal side effects: pain, fatigue, headaches. But many of the new Covid-19 vaccines are more likely to cause these kinds of side effects than you might be used to. Particularly after the second dose. Most people will feel a little pain in their arm. Many will be tired and get headaches.

Obviously, having no side effects is desirable. But with the spike protein of the coronavirus, it really does elicit some side effects. But that’s totally normal. And once you understand why vaccine side effects happen, you might actually be happy to get them. 

First, we have to talk about this: your immune system, which is a huge network of different cells and proteins in your body. You’ve got things like:

• white blood cells that fight the invading virus or bacteria, 
• communication cells that organize the response, and 
• antibodies that search for and identify the enemy.

When, a virus attacks your body, your immune system attacks back. Your body increases blood flow to get more of these battle cells in circulation. Your temperature might go up, too, as one of the tactics your body has to help kill the invaders. And after your white blood cells destroy the virus, they produce antibodies that will identify the virus should it reappear in the future, and remember how to fight it. This is how you gain immunity. 

This response is actually what gives you a lot of the symptoms you feel when you catch, for example, the common cold. But the cold virus doesn’t give you a fever, or a runny nose, or body aches — your immune system does, while fighting the virus. And triggering this system, without actually getting you sick, is how vaccines work.

Most vaccines are made up of a weakened or dead pathogen, or a portion of one. Or, in some of the new Covid-19 vaccines, the genetic code of a portion of one, either in the form of DNA, or what’s called messenger RNA, along with minor ingredients to keep it stable. It’s harmless, but when your immune system detects it, it responds just like it’s a real danger. It attacks the intruder, and creates those memory antibodies to be able to fight it again in the future. 

Vaccines are designed to give you the same immunity as if you had fought off the real virus. And some of the new Covid-19 ones do this particularly well. The messenger RNA vaccines are quite good at stimulating your immune system. That's why you have ninety-five percent efficacy. That’s right — a 95% chance of being protected against Covid-19. That makes them some of the most effective vaccines. But that also means they’re really good at activating your immune system. Which means your body will increase blood flow to where that vaccine is, which is why pain at the injection site is so common. Your body might even think, better turn up the heat, and then you get a fever, or the chills. So experts emphasize that we should look at most side effects as a good thing: it means the vaccine is working. 

When we talk about these common reactions to vaccines, like fever and fatigue, we’re mostly talking about the mild-to-moderate ones. These are the lowest of the side effect categories that health regulators use, the kind you get over in a day or two. 

Then there’s severe side effects — the type that might make you call in sick to work or call a doctor. These were rare in the clinical trials for the first two studied vaccines to become available, with the exception of some severe fatigue and muscle pain on the second dose. And that’s because if these vaccines were dangerous, they’d never reach the public in the first place. We really don't accept any sort of permanent, serious harm from a vaccine, nor should we. 

News stories that imply otherwise can be scary, but they get more attention than they probably deserve. Like one about a serious allergic reaction. It may have occur in someone with a history of serious allergic reactions. Or about someone dying after getting a second dose of the vaccine. When, it turned out, other factors had caused his death. 

In fact, no deaths have been reported from the millions of doses that have been given out. And the controlled studies with thousands of people found the same thing: no deaths from the vaccine. These vaccines aren’t just safe — they’re life savers. 

You should be skeptical of anything you put in your body, including vaccines. But once you've seen the data, and you see that there wasn't a serious side effect before approval, and hasn't been a serious side effect post-approval, then I think you should be convinced. Basically, you want to reduce where the virus can go. And if you immunize as many people as possible, that pool of people that it can transmit to becomes less and less and less and less..!

Vaccines are the way out of the Covid-19 pandemic. And, like with all vaccines, many of us who get it will also feel a little merely for a day or two. But the scientists who have studied these vaccines — who have seen the side effects — are some of the most eager to get it... I hope now you must have got some motivation for getting yourself jabbed. So, get up and get your shot as soon as possible...!!

How vaccines work with immune system to protect us from infection?

A vaccine is a type of medicine that is designed to stimulate our immune system against a specific pathogen, such as a virus or bacterium, so that we are protected from illness if we come into contact with that pathogen in the future. Vaccines have an important role in protecting us from infectious disease. 

But how do the vaccines work? 

Well, put simply, vaccines train our immune system to detect and attack pathogens. Here is a little explanation of how they do it, from start to finish. 

Our immune system is incredibly impressive..! It is a marvellously complex network of molecules and cells, which has the power to destroy pathogens like viruses and bacteria. There are two general sides of the immune system coin the innate immune system and the adaptive immune system. You're born with an innate immune system that is essentially ready to roll and you develop your adaptive immune system over time by exposure to various pathogens. The innate immune system is rapid and non-specific. 

The part of the immune system that vaccines train is  adaptive immune system. It’s first job is to recognize an invader. In the case of this bacterium it does this by detecting molecular markers called antigens, that are part of all pathogens. After detecting an antigen, the adaptive part of the immune system starts mounting a bespoke response. 

B-cells convert to plasma cells, and start creating proteins called antibodies, which bind specifically to the antigen. Together with immune cells called phagocytes, antibodies can destroy the pathogen. The adaptive immune system also produces Killer T cells, which have the ability to detect and destroy cells infected with the pathogen. 

But it doesn’t end there - to prevent against future infections, the adaptive immune system also has a memory. It produces long lived memory cells, which lie in wait ready to pump out the right antibodies and killer T cells if the same pathogen is ever seen again. This is called immunity. 

Vaccines work by activating the adaptive immune system and so creating immunity. They safely introduce antigens for the immune system to train on, preparing itself to fight real infections in the future.

So what actually goes into a vaccine?

Well, there are several different types. 

One of the most common are called live-attenuated vaccines. These include things like MMR (measles, mumps, and rubella combination vaccine) or BCG (bacille Calmette-Guerin---a vaccine for TB). Live attenuated vaccines work by introducing a weakened version of a living pathogen into the body. These attenuated pathogens are not strong enough to cause disease in people with healthy immune systems, but they can still trigger a strong immune response. Live attenuated vaccines trigger a similar immune response to a real infection, leaving behind the same memory cells. This means that some can provide a life-time of protection after just one or two doses. 

Another key type of vaccine is called a subunit or recombinant vaccine - they work differently. Instead of a live sample, subunit vaccines contain only part of the pathogen. For instance the vaccine for Human Papilloma Virus, HPV uses hollow virus-like particles made from a protein found in HPV. Alone, these subunits cannot get the immune system’s attention, and so they need a bit of help from another ingredient - an adjuvant.

Adjuvants wake up the immune system, triggering it to see the subunit antigens and start creating antibodies and memory cells. Subunit vaccines contain no live pathogens, and so lack the genetic information needed to replicate. That means that they are not infectious and are safe even for people with weakened immune systems.

But generally, they don’t trigger the production of as many memory cells, compared to live attenuated vaccines - and so they don’t provide such long lasting protection. Training the immune system through vaccination helps to protect individuals from infection. But vaccines can also protect people who can’t receive them. This is called herd protection or herd immunity.

Herd immunity is created when a large percentage of a population is immune to a disease. It works by disrupting chains of infection. Without new hosts to infect, pathogens can’t survive. That means that if a pathogen tries to infect someone who is vaccinated and so immune, it dies and the chain of infection is broken. 

If enough chains are broken in a population, it becomes very difficult for pathogens to reach those who would be vulnerable. Herd immunity protects millions of people around the world, but if vaccination rates drop, there is a risk that diseases can reappear. For example, measles was declared eradicated in the United States in 2000, but since then, falling vaccination rates have led to a resurgence of the disease with outbreaks recorded in 31 states. 

If herd immunity is maintained for long enough though, diseases can be eradicated completely. For example smallpox, which is estimated to have killed 300 million people in the 20th century, is now considered extinct. 

All thanks to vaccination, its training regime and the wonders of herd immunity.

 STAY SAFE AND GET FULLY JABBED AS SOON AS POSSIBLE..!