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.

Booster Shots? Are they necessary for COVID?

At the moment a lot of countries have high vaccination rates, but there are questions being asked about whether the third doses -known as BOOSTER SHOTS may be necessary, but of course as with much to do with COVID the evidence is still emerging. 

What are BOOSTER SHOTS?

Well, the vaccines we have all do a pretty good job of introducing our bodies to certain diseases and convincing our  immune systems to take that threat seriously. But for some diseases, it takes extra convincing. Which is why you might need to get the same shot more than once -weeks or even years later.

Vaccines teach our immune systems to recognize  certain pathogens, or disease-causing agents. In a nutshell, they trigger the formation  of specialized cells and antibodies that recognize the distinctive proteins that  stick out of pathogens -called antigens. If something with one of those antigens shows  its face, the antibodies latch on and disable it,  while those specialized cells  help to kick it to the curb.

Now, there are a few vaccines that  require multiple doses of the same shot. And there are almost as many reasons  for that as there are different vaccines. Because how much immunity you get from a single  shot, and how long it lasts, can really vary.

Are Booster shots necessary for COVID?

The short answer is, IT'S UNCLEAR.! 

We do know, and this is very early evidence, that antibody levels tend to fall in the weeks and months following a second shot. And this is obviously complicated by the highly infectious Delta variant. But what's important to remember is that antibody levels aren't the only part of our immune system that help give us protection. So we have other, sort of, immune system soldiers like B-cells and T-cells, that all together help provide that protection. 

At the moment, scientists don't quite know what level of antibodies, what level of B-cells and T-cells are necessary to give us that protection that we're looking for. So just because the antibody levels may be falling, that does not mean that our bodies won't remember how to deal with this enemy if we come across it in the weeks and months following the second shot. 

In the UK, for instance, we do have data that suggests that antibody levels are falling in fully vaccinated people in the weeks and months after their second dose. 

However, it does not appear to have directly translated into higher hospitalizations and deaths in in that category of people. Of course the argument for people who are you know compromised or are classed test clinically vulnerable is far stronger, and that's because after getting two shots, they don't get the optimum level of protection as the rest of us do, and so it does make sense to top up that already, sort of, lower level of protection that this category of people may have gotten post their first two shots. 

Overall, though, whether we’ll need booster shots down the line depends on a few things, like how much our immunity declines.  

Does a booster shot need to be the same as my vaccine?

No, not necessarily, and that's pretty much what scientists are trying to figure out. 

The general prevailing hypothesis is that given the different vaccines teach the immune system to recognize the enemy in this case the virus in different ways, if you provide different doses of the different vaccines, that might potentially lead to a more diverse, broader sort of immunity. 

But much like everything else, the science is still ongoing, and we don't really have a  good answer for this yet. 

On the safety side, there are worries, and early evidence from the UK suggests that mixing and matching the jabs does tend to increase the rate of side effects, and so that is something that policy makers will have to contend with. 

In short, we’re going to need a lot more  information before we know exactly how often we’re going to need to be vaccinated against COVID-19 and how much those vaccines will need to change.

The good news is, scientists are on the  case. Immunology is complicated, But we’re getting better against COVID-19.

STAY SAFE AND FOLLOW PRECAUTION.

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..!

New Covid-19 Cases Raise Concerns About Immunity

Throughout the pandemic, athletes have been the most tested population on the planet, sometimes providing examples of emerging theories about COVID-19. And as countries around the world continue to fight back COVID-19, attention has turned to Tokyo where the Olympics are under way. One challenge some athletes are facing: testing positive for the virus, despite having been vaccinated. This isn't the first we've heard of this.

What are chances of getting COVID-19 after receiving a vaccine?

Well, you've got a better chance of buying a winning lottery ticket but it happened to Warriors player Damion Lee. He will be out at least two weeks. It was not a false positive as first thought, even though Walman had been vaccinated. Yankees GM Brian Cashman says that three players tested positive and three others are likely infected. About 85% of the team is vaccinated, including those who have the virus.

These examples are known as breakthrough infections, which occur when someone tests positive for COVID-19 at least two weeks after getting their final shot.

Do these breakthrough cases mean the vaccines are failing?

No, the vaccines are not failing. The vaccines are working extremely well, and as expected. They do protect the majority of recipients from severe disease. That's what vaccines are designed to do: Prevent death and severe disease.

But most vaccines, including those created to fight COVID-19 don't completely protect you from infection. So it's not all that surprising that breakthrough infections are showing up. As of July 12th, more than 159 million people in the US have been fully vaccinated. CDC data suggests just under 5,500 have had breakthrough infections, resulting in hospitalizations or deaths. That's one in approximately 29,000 people who have been vaccinated.

Breakthrough infections are something that we want to monitor but in terms of their overall influence in the pandemic, they play a much smaller role than transmission among people who haven't been vaccinated. But these cases raise questions about our immunity to the virus and hint at a future in which it isn't gone completely and we learn to live with it. That's due in part to variants.

Research shows that variants, including Delta, can partially evade the immune response from prior infection and vaccination. We mount a really good immune response against the virus that our body's trying to recognize. Your body is really good at recognizing and neutralizing those specific threats. But when the virus starts to change, sometimes it doesn't recognize the virus as well. And so that's how you sort of see it chip away at that immune response. That's one of the reasons that health officials are really sort of concerned about this global vaccination drive in order to prevent the virus from spreading, both to save lives and to prevent it from further mutating and evading immune response.

The Delta variant is the most contagious version of the virus to be identified, but research suggests that full vaccination is still protective against severe disease and death: the outcomes that have made COVID-19 so devastating. 

What dictates whether someone is more likely to get infected, even if they're vaccinated?

Dr. Hatziioannou says there are four main variables. 

First is the amount of virus that is circulating in your community. So if a great number of people around you are infected, then the possibility of you getting exposed obviously increases. If you're in close proximity with people that are infected, particularly those that are unvaccinated and have generally higher viral loads, then the probability of you getting infected increases.

Second is tied to vaccine uptake, So if a large proportion of the population is vaccinated, then your virus transmission, virus loads, everything decreases. So the chances of spreading the virus amongst this population obviously decreases. That's because vaccinated people act as a kind of shield, even when they do get infected. A recent CDC study found that vaccinated people carried less virus and potentially didn't spread it as much as unvaccinated people. Cases were also shorter and less severe. Vaccines help create a kind of immune memory of what a virus looks like, helping the body fight it off more quickly when it spots it. That makes it harder for the virus to spread overall. Roughly half of all Americans are fully vaccinated but in some states and globally, the vaccination rate is much lower, giving the virus more opportunity to spread and mutate. That's why having large gathering, like concerts or the Olympics can be so challenging from a public health perspective.

Third, individual behavior matters. So as measures have been abandoned, such as masking and social distancing, when you don't have a significant number of the population vaccinated, then the ability of the vaccines to protect you from getting infected decrease.

Finally, even after vaccination, individual immune systems vary in their ability to prevent and fight off infection. Older and immunocompromised people seem to be more susceptible to breakthrough cases, and those tend to be severe. That's why health officials are considering additional doses right now, primarily for people who have a compromised immune system and might not have produced a good immune response after two doses of the vaccine.

Breakthrough cases might be asymptomatic or mild, so people may not know to get tested. But that's not the case for athletes. We're actually seeing breakthrough infections happen a lot more amongst sports teams, like baseball or for the Olympics because those are the people that get tested pretty regularly, even if they're vaccinated.

At the Olympics, organizers of the games are scrambling to deal with a rising load of athletes and officials who are testing positive upon arrival in Japan, some with breakthrough infections. The vaccination rates are low in Japan. Cases there are rising and organizers didn't require those participating to get vaccinated.

Dr. Hatziioannou and many other experts remain concerned that holding a large-scale international event prior to reaching a critical mass of vaccinated individuals has the potential to contribute to the virus's spread around the world. The Olympics is a special event and it's truly remarkable that it brings all these people from all these different countries together but it also poses a perfect ground to mix variants and spread the virus that will then go back to each athlete's country.