Information

How do viral vaccines work?


I have read that a vaccine against a pathogen typically works by using a dead or weakened version of that pathogen and then inciting an immune response against the pathogen so that the immune system then recognizes that pathogen in the future and attacks it immediately.

However, suppose that a person gets vaccinated against a virus. Why couldn't the virus infect a few cells before it runs into immune system cells and starts replicating as normal? Does the immune system somehow recognize virus-infected cells?

Also, how would a vaccine against a virus that attacks immune system cells work (like HIV, for instance)? In this scenario, wouldn't any immune cell that tries to destroy the virus get infected itself?


Vaccines containing these weakened or killed viruses or bacteria are introduced into your body, usually by injection. Your immune system reacts to the vaccine in a similar way that it would if it were being invaded by the pathogen - by making antibodies. The antibodies react to the vaccine (virus/bacteria) just as they would the live pathogen - like a training exercise against an antigen. Then they stay as amemory in your body, giving you immunity. If you are ever exposed to the real disease, the memory is activated and antibodies are there to protect you.

Moreover if a cell gets infected virally, infected cells produce and release small proteins called interferons, which play a role in immune protection against viruses. Interferons prevent replication of viruses, by directly interfering with their ability to replicate within an infected cell.


It depends on the particular vaccine. Generally we can divide vaccines into two groups: live and "dead".

Live vaccine contains weakened (attenuated) pathogen, which (in case of a virus) theoretically can infect our cells. However, as it is attenuated, it is not doing it very efficiently, thus even naive immune system has no problem with defeating it.

"Dead" vaccines contain either inactivated ("killed") pathogen or only some of its parts (antigens). As it is not active virus, it can not infect your cells. It is just presented to your white blood cells as a "dummy" for "target practice". And by "target practice" I mean things like activation and proliferation of competent lymphocytes, followed by formation of immunological memory - exactly as if the organisms was infected by a virus.

Our body is "blindly" creating a variety of lymphocytes, and each of them is able to fight with pathogens with certain antigens. As the lymphocytes has been created "blindly", most of them seems to be useless. However, if there happens to be a lymphocyte able to recognize a virus antigen, the lymphocyte is indeed useful. It proliferates, "learns" to recognize the antigen even better, fights the virus (or its antigens) and is preserved as memory cells, just in case of reinfection.

Of course I am oversimplifying here, but I hope I managed to grasp the big picture. ;)


Dr. Garman explains how COVID-19 mRNA vaccines work

UPDATE: The FDA authorized a third COVID-19 vaccine in late February.

So far, the Food and Drug Administration has authorized two COVID-19 vaccines — the Pfizer-BioNTech COVID-19 vaccine and the Moderna COVID-19 vaccine​​ — which are both messenger ribonucleic acid or mRNA vaccines.

The Centers for Disease Control (CDC) describes these mRNA vaccines as containing instructions for your cells on how to make a piece of the “spike protein” that is unique to COVID-19. That protein triggers an immune response inside our bodies, producing antibodies and activating T-cells to fight off what it thinks is an infection. This protects us from getting infected if the real virus enters our bodies. The CDC points out that mRNA vaccines do not use the live virus that causes COVID-19.

NDWorks asked Dr. Ben Garman , medical director at the Notre Dame Wellness Center, to explain how mRNA vaccines work.

“An mRNA vaccine works a little differently than most other vaccines that are available to us, such as a more traditional mechanism of vaccination for the measles or the flu or chickenpox. Typically, those either use a weakened, killed or a picked-apart copy of the virus that won’t normally cause you to contract disease, but it's similar enough to the real virus or bacteria that your body mounts an immune response to the real version.

“The way these new mRNA vaccines work is the mRNA molecule is surrounded by a lipid shell or kind of a chunk of fat, and all that chunk of fat does is allow that mRNA molecule to enter your cells, otherwise mRNA can't get past the membrane. And once it's there, your body reads that mRNA and uses its natural machinery to produce a specific protein that would naturally be on the virus that you are vaccinating against — in this case, the spike protein, which a lot of people have probably heard of for COVID. Your body naturally recognizes that spike protein, after your cell makes it, as something bad. And it makes a bunch of immune responses to that spike protein without you ever having to have the virus inside your body .

“. mRNA vaccines have a lot of benefits compared to traditional mechanisms. One of those benefits (to scientists and doctors) is that all you need to start working on (the vaccine) is the genetic code of the virus. And that genetic code was known by December of 2019. And so (scientists and doctors) could start producing potential variations of this vaccine even before 2020 started, and they did. Moderna, specifically, is a company founded to make mRNA vaccines, and so this is all they do. This is the first commercial mRNA vaccine, but it's not the first mRNA vaccine that they've ever tried or have done research on. It's still a relatively new form of technology, but this is not the first. This is just the first one that is for commercial use.”

Dr. Garman points out that mRNA vaccines will not affect your DNA.

“It's not going to change your genetic material. It's just that temporary blueprint. And then using the natural mechanisms of your body, you then produce a specific protein that's normally on the virus,” he said.


Messenger RNA (mRNA) provides a recipe that your cells can use to make proteins. SARS-CoV-2 vaccines include instructions to make one portion of the virus (the spike protein) that is harmless by itself. After injection, the cells in your arm muscles pick up the mRNA, make the protein, and display it on the cell's surface. Your immune system sees the protein and learns how to make an immune response against it. If you are infected with SARS-CoV-2, your immune system recognizes the same spike protein and can quickly induce an immune response to fight the virus.

Safety: Unlike live-attenuated or viral-vectored vaccines, mRNA is non-infectious and poses no concern for DNA integration—mainly because it cannot enter the nucleus which contains DNA. Other strategies such as protein-based or inactivated vaccines also require chemicals and cell cultures to produce. mRNA is made through a cell-independent process and does not require inactivation thus, it poses no safety concerns due to contamination with toxic agents.

Efficacy: mRNA is rapidly degraded in the body, and cells don't readily take up foreign mRNA. Recent technology has modified the mRNA molecule to make it more stable and packaged the molecules in fats (called lipids), increasing cell delivery efficiency. These advances increase the amount of spike protein produced on your cells, thereby stimulating a more effective immune response.

Production: mRNA can be quickly designed and scaled up, if necessary. The manufacturing is sequence-independent, which makes it highly adaptable to different pathogens. The cost is also lower than other platforms and will continue to decrease as the technology expands.


How do scientists develop vaccines for new viruses?

Viruses and the immune system interact in complex ways, so there are many different approaches to developing an effective vaccine.

Published: 26th May, 2020 at 11:00

Vaccines work by fooling our bodies into thinking that we’ve been infected by a virus. Our body mounts an immune response, and builds a memory of that virus which will enable us to fight it in the future.

Viruses and the immune system interact in complex ways, so there are many different approaches to developing an effective vaccine. The two most common types are inactivated vaccines (which use harmless viruses that have been ‘killed’, but which still activate the immune system), and attenuated vaccines (which use live viruses that have been modified so that they trigger an immune response without causing us harm).

A more recent development is recombinant vaccines, which involve genetically engineering a less harmful virus so that it includes a small part of the target virus. Our body launches an immune response to the carrier virus, but also to the target virus.

Over the past few years, this approach has been used to develop a vaccine (called rVSV-ZEBOV) against the Ebola virus. It consists of a vesicular stomatitis animal virus (which causes flu-like symptoms in humans), engineered to have an outer protein of the Zaire strain of Ebola.

Vaccines go through a huge amount of testing to check that they are safe and effective, whether there are any side effects, and what dosage levels are suitable. It usually takes years before a vaccine is commercially available.

Sometimes this is too long, and the new Ebola vaccine is being administered under ‘compassionate use’ terms: it has yet to complete all its formal testing and paperwork, but has been shown to be safe and effective. Something similar may be possible if one of the many groups around the world working on a vaccine for the new strain of coronavirus (SARS-CoV-2) is successful.


Assessment Questions

__________ refers to the protection offered to everyone in a community by high vaccination rates.

  • Infection
  • Herd immunity
  • Community immunity
  • Both a and b
  • Both b and c

The polio vaccines developed by Jonas Salk and Albert Sabin in the mid-20th century were made using __________ cells.

True or false? Exposing a child to wild chickenpox puts him or her at risk for a severe case of the disease.


COVID-19 Vaccines: Infographic

mRNA is a molecule that tells our bodies to make proteins. mRNA from the COVID-19 virus tells our cells to make harmless proteins just like those on the virus. The Pfizer and Moderna vaccines work this way.

Protein subunit vaccines, such as the Novavax vaccine, contain harmless pieces of proteins unique to the COVID-19 virus.

Vector vaccines, like the AstraZeneca vaccine, use another virus that has been made safe. Material from the COVID-19 virus has been inserted inside of it. The material tells our cells to make harmless proteins unique to the COVID-19 virus.

What to expect when you get vaccinated

The Pfizer, Moderna and AstraZeneca vaccines are given as two shots in the upper arm muscle, three or four weeks apart.*

Typically, it takes about two weeks after the second shot for sufficient immunity to kick in.

Even after the vaccination, you might be able to pick up the virus, carry it and give it to others so infection prevention measures are still very important.

Are the vaccines safe?

Do the vaccines work?

  • Based on clinical trials, the first two vaccines were shown to be extremely effective at preventing COVID-19: Pfizer (95%) and Moderna (94.1%).*
  • The trials so far show the vaccines are equally effective across age,** gender, race and ethnicity subgroups.
  • The clinical trials were conducted with a diverse group of participants, including people of Asian, Black, Hispanic/Latinx and Native American descent.***

*As additional clinical trials are completed, we will know more about the efficacy of other vaccines. **The Pfizer vaccine was found to be over 94% effective in adults over the age of 65. ***Among the Pfizer participants, 5% were Asian, 10% were Black, 26% were Hispanic/Latinx and 1% were Native American. Among the Moderna participants, 4% were Asian, 10% were Black, 20% were Hispanic/Latinx and 3% were of other descent.

IMPORTANT VACCINE FACTS

The truth: You will not get COVID-19 from the vaccine.

The truth: The vaccine will not change or damage your genetic information.

The truth: Even if you are vaccinated, you should still wear your mask, frequently wash your hands and maintain physical distance to help keep everyone safe.


Contents

Attenuated viruses Edit

Viruses may be attenuated using the principles of evolution via serial passage of the virus through a foreign host species, such as: [8] [9]

The initial virus population is applied to a foreign host. Through natural genetic variability or induced mutation, a small percentage of the viral particles should have the capacity to infect the new host. [9] [10] These strains will continue to evolve within the new host and the virus will gradually lose its efficacy in the original host, due to lack of selection pressure. [9] [10] This process is known as "passage" in which the virus becomes so well adapted to the foreign host that it is no longer harmful to the subject that is to receive the vaccine. [10] This makes it easier for the host immune system to eliminate the agent and create the immunological memory cells which will likely protect the patient if they are infected with a similar version of the virus in "the wild". [10]

Viruses may also be attenuated via reverse genetics. [11] Attenuation by genetics is also used in the production of oncolytic viruses. [12]

Attenuated bacteria Edit

Bacteria is typically attenuated by passage, similar to the method used in viruses. [13] Gene knockout guided by reverse genetics is also used. [14]

Attenuated vaccines can be administered in a variety of ways:

  • Injections:
    • Subcutaneous (e.g. measles, mumps and rubella vaccine, varicella vaccine, yellow fever vaccine) [15]
    • Intradermal (e.g. tuberculosis vaccine, smallpox vaccine) [15]
    • Nasal (e.g. live attenuated influenza vaccine) [16][15]
    • Oral (e.g. oral polio vaccine, recombinant live attenuated cholera vaccine, oral typhoid vaccine, oral rotavirus vaccine) [15][17]

    Vaccines function by encouraging the creation of cells, such as CD8+ and CD4+ T lymphocytes, or molecules, such as antibodies, that are specific to the pathogen. [7] The cells and molecules can either prevent or reduce infection by killing infected cells or by producing interleukins. [7] The specific effectors evoked can be different based on the vaccine. [7] Live attenuated vaccines tend to help with the production of CD8+ cytotoxic T lymphocytes and T-dependent antibody responses. [7] A vaccine is only effective for as long as the body maintains a population of these cells. [7] Live attenuated vaccines can induce long-term, possibly lifelong, immunity without requiring multiple vaccine doses. [10] [7] Live attenuated vaccines can also induce cellular immune responses, which do not rely solely on antibodies but also involve immune cells such as cytotoxic T cells or macrophages. [10]

    Live-attenuated vaccines stimulate a strong and effective immune response that is long-lasting. [3] Given pathogens are attenuated, it is extremely rare for pathogens to revert to their pathogenic form and subsequently cause disease. [18] Additionally, within the five WHO-recommended live attenuated vaccines (tuberculosis, oral polio, measles, rotavirus, and yellow fever) severe adverse reactions are extremely rare. [18] However, similar to any medication or procedure, no vaccine can be 100% safe or effective. [19]

    Individuals with compromised immune systems (e.g., HIV-infection, chemotherapy, combined immunodeficiencies) typically should not receive live-attenuated vaccines as they may not be able to produce an adequate and safe immune response. [3] [18] [20] [21] Household contacts of immunodeficient individuals are still able to receive most attenuated vaccines since there is no increased risk of infection transmission, with the exception being the oral polio vaccine. [21]

    As precaution, live-attenuated vaccines are not typically administered during pregnancy. [18] [22] This is due to the risk of transmission of virus between mother and fetus. [22] In particular, the varicella and yellow fever vaccines have been shown to have adverse effects on fetuses and nursing babies. [22]

    Some live attenuated vaccines have additional common, mild adverse effects due to their administration route. [22] For example, the live attenuated influenza vaccine is given nasally and is associated with nasal congestion. [22]

    Compared to inactivated vaccines, live-attenuated vaccines are more prone to immunization errors as they must be kept under strict conditions during the cold chain and carefully prepared (e.g., during reconstitution). [3] [18] [20]

    The history of vaccine development started with the creation of the smallpox vaccine by Edward Jenner in the late 18th century. [23] Jenner discovered that inoculating a human with an animal pox virus would grant immunity against smallpox, a disease considered to be one of the most devastating in human history. [24] [25] Although the original smallpox vaccine is sometimes considered to be an attenuated vaccine due to its live nature, it was not strictly-speaking attenuated since it was not derived directly from smallpox. Instead, it was based on the related and milder cowpox disease. [26] [27] The discovery that diseases could be artificially attenuated came in the late 19th century when Louis Pasteur was able to derive an attenuated strain of chicken cholera. [26] Pasteur applied this knowledge to develop an attenuated anthrax vaccine and demonstrating its effectiveness in a public experiment. [28] The first rabies vaccine was subsequently produced by Pasteur and Emile Roux by growing the virus in rabbits and drying the affected nervous tissue. [28]


    Your immune system is like an army

    Think of your body’s immune system as an army. Giving an inactivated vaccine is like holding up the uniform of an enemy soldier in front of your body’s immune system and saying, “See this, everybody? You go seek and destroy everybody wearing this.” Giving a live/attenuated vaccine is like finding an enemy soldier, beating the crap out of him and putting it in front of your body’s immune system and saying, “See this guy right here? You go beat the hell out of anything and anybody who looks like him.” Now, if somebody has a compromised immune system, the beat-up bad guy can still cause a lot of damage, which is why people who are immunocompromised or have a weak immune system shouldn’t get live/attenuated vaccines.

    So is the flu vaccine live? No. The flu vaccine is inactivated it’s dead. It is nothing more than the protein coat of influenza with all of the DNA removed. It is an empty shell of a uniform.


    2 New COVID-19 Vaccines: Here's How They Work

    Both of these vaccines share some similarities with those already being delivered, but they also have some notable differences. Here, let’s take a look at how they work and how effective they could be.

    Thanks to the efforts of scientists, healthcare workers and trial participants around the world, a number of COVID-19 vaccines have now been authorised for general use. But while millions have been given a jab, billions still need to be vaccinated. We need to produce as many doses as we can.

    So, it’s good news that two additional vaccines are on the horizon. Vaccine developers Novavax and Johnson & Johnson recently released data from the phase 3 clinical trials of their jabs, which will hopefully join the list of those approved later this year.

    Both of these vaccines share some similarities with those already being delivered, but they also have some notable differences. Here, let’s take a look at how they work and how effective they could be.

    Johnson & Johnson

    The Johnson & Johnson vaccine is being tested in 44,000 people across the US, Brazil and South Africa. Preliminary data suggests the amount by which it reduces the risk of moderate to severe COVID-19 (its efficacy) is 66%, four weeks after vaccination.

    This figure might suggest that the vaccine isn’t as good as the Pfizer/BioNtech and Moderna jabs, which in trials reduced the risk of developing symptomatic COVID-19 by over 90%. However, its phase 3 trial started in November 2020, meaning the vaccine came up against some of the new, tougher variants of the coronavirus during testing. Indeed, its efficacy against B1351, the variant first found in South Africa, was only 57% – but some the authorised vaccines are less effective against this variant too.

    One-third of trial participants were over 60, and the vaccine seems to work just as well in them as in younger people. This is good news, given the recent questions over how effective the Oxford/AstraZeneca vaccine is in older people.

    But perhaps the most important point is that none of those given the Johnson & Johnson vaccine died or were admitted to hospital with COVID-19. The results also show the vaccine reduced the risk severe of disease by 85%.

    The vaccine’s design is similar to the Oxford/AstraZeneca one. It focuses on a particular part of the coronavirus that we think triggers a protective immune response – the spike protein, which sticks up on the virus’s surface. The genetic code for just the coronavirus’s spike protein has been put into a harmless strain of another virus – an adenovirus, called Ad26 – which has been altered so it can’t cause disease. It can, though, still get inside our cells. When it does, the cell reads the genetic code for the spike protein and produces lots of copies of the protein. The immune system then mounts a response to these.

    In the trials, researchers found that people assessed 28 days after receiving one dose showed a strong immune response. So, Johnson & Johnson is seeking approval for a single-dose regime (all of the vaccines authorised so far require two doses). However, they are continuing with tests to see whether giving two doses makes a difference.

    It would be great if one dose was enough: more people could be given the vaccine sooner. The UK has ordered 30 million doses, which using a one-dose regime would cover half the country’s adults.

    The Novavax COVID-19 vaccine is a little bit different. It still uses the idea of taking the genetic code for the spike protein and putting it into another virus, but in this case the “carrier” virus is one that infects insects, a baculovirus. It’s used to infect moth cells, which go on to produce copies of the spike protein. These are then harvested and purified into a vaccine to give to people. So instead of our bodies making copies of the spike protein to stimulate the immune system, with this vaccine the proteins arrive ready-made.

    This method may sound a bit weird, but it’s a very standard way of making proteins for experiments in biology. It’s been around for over 30 years.

    The phase 3 trial of Novavax’s vaccine involved 15,000 people and was run in the UK. Preliminary analysis shows that 62 participants developed symptomatic COVID-19: 56 in the placebo group and just six in the vaccine group. This makes the estimated efficacy 89%.

    Some of the 56 patients in the placebo group were found to have the more infectious B117 variant of the virus that arose in the UK. This shows that volunteers were exposed to this variant and suggests that the vaccine will protect against it. Meanwhile, in a separate trial in South Africa, the vaccine was shown to reduce the risk of symptomatic disease by 60%. This suggests it will be relatively effective against the problematic B1351 strain too.

    If authorised, the vaccine will be manufactured in the UK. Currently, Britain has 60 million doses on order, which again is enough to vaccinate half the adults in the country.

    It’s important to remember that for both vaccines, the figures quoted are from the first detailed look at the trial results. More calculations are still to be done and everything has to be reviewed by other scientists (peer review), so the final numbers may change.

    We also don’t know yet if these vaccines will limit viral transmission or just limit people from developing disease, nor how long their effects will last. But in a way, it doesn’t matter. Really, we need vaccines to help get the pandemic under control in the short term, and the more options we have, the faster we can move towards this.

    Some vaccines will probably be chosen by some countries because they work better in particular age groups or against certain strains, or because they are easier to transport. These two can be stored in a normal fridge so, unlike some COVID-19 vaccines, they could be easily used anywhere in the world.

    Sarah Pitt, Principal Lecturer, Microbiology and Biomedical Science Practice, Fellow of the Institute of Biomedical Science, University of Brighton

    This article is republished from The Conversation under a Creative Commons license. Read the original article.