Science Series #12: COVID-19 Vaccines

How do COVID-19 vaccines work?

COVID-19 vaccines allow the immune system to develop antibodies against the virus prior to coming in contact with the illness. Vaccination exposes the body to infectious foreign antigens, which are the spike proteins of the SARS-CoV-2 that lead to the onset of antibody production and immune system activation. Hence, upon vaccination, the body will be left with T-lymphocytes and B-lymphocytes that have a memory in fighting the virus in the future. Developing immunity through vaccination reduces the severity of COVID-19 and the risk of developing the illness and its consequences. Additionally, it reduces the risk of transmitting the disease to other people.

Vaccines Remain Of Vital Importance In Preventing The Spread Of Infectious Diseases And Have Saved Millions Of Lives

(Source: Centers for Disease Control and Prevention, U.S. Food and Drug Administration, World Health Organization)

What are the different types of COVID-19 vaccines?

All vaccines expose the body to molecules from the pathogen in order to trigger an immune response. However, the method of exposure varies. Generally, there are four different types of vaccines:

Whole virus vaccines use a deactivated form of the virus or pathogen, which triggers an immune response. There are two main types of whole virus vaccines:
  • Inactivated vaccines use the destroyed genetic material of the virus in order to prevent the infection and replication of cells within the body while still causing an immune reaction. Inactivated vaccines still contain many proteins the body can react to; however since they cannot infect cells, they only stimulate antibody-mediated responses. Since these responses may be less long-lived and weaker, most of these vaccines are given either with adjuvants, which stimulate the immune system, or require booster doses.
  • Live-attenuated vaccines use a live but deactivated or weakened pathogen, hence they can grow and replicate without causing the illness. Because these vaccines contain a weakened version of the pathogen, the immune system responds as it would towards another pathogen through its natural defense mechanism of producing antibodies. The immune response remains until the virus is completed out of the body; hence this allows time for the development of memory cells against the virus.

Protein subunit vaccines include small fragments or isolated proteins of the virus that cause COVID-19 instead of the whole virus. These fragments are specifically selected based on their ability to trigger an immune reaction. Upon vaccination, the body recognizes the foreign protein and begins to build antibodies and T-lymphocytes that create an immunological memory. This mechanism reduces the risk of side effects, yet weakens the immune response. Hence, they also often require adjuvants.

Viral vector vaccines use a modified, safe version of a different virus, also known as a vector, to deliver instructions to the cells. The vector is not the COVID-19 virus itself; rather it is a similar, harmless virus that delivers genetic instructions and uses the cells machinery to produce copies of the spike proteins known to cause COVID-19. To do this, the pathogenic spike proteins are inserted into a safe virus, which serves as a platform to deliver the protein into the body. These vector viruses are stripped from their disease-causing genes or genes that cause their replication usually through heat, making them safe. Once the body encodes the genetic instructions from the vector and replicates the spike proteins, they become displayed on the surface of the cells. Then, the immune system recognizes the foreign proteins and begins the onset of antibody production to fight COVID-19 upon infection. These vaccines can mimic a natural viral infection, leading to triggering a strong immune response. However, the effectiveness of these vaccines may decrease if the individual was already exposed to the virus used as the vector. To date, the COVID-19 viral vectors used are non-replicating, meaning that they are unable to make new viral particles but only produce the antigen.

mRNA vaccines are a rather new approach towards vaccinations, as prior to the COVID-19 pandemic, none had gotten full approval. Rather than using a weakened pathogen or modified versions of the virus, these vaccines use a section of genetic material (mRNA) to provide instructions to the cells on how to make copies of the antigen that cause the virus. Since the antigen is produced in the cells, the immune response should be strong. The COVID-19 mRNA vaccines give cells the instructions to produce harmless “spike” proteins, then the mRNA instructions are quickly degraded. Next, the cells present this protein on its surface which get recognized by the immune cells as foreign, allowing the onset of an immune response, similar to what happens in a natural infection against COVID-19. By the end of the process, the body is able to respond to the virus by its newly acquired ability to recognize and attack the spike proteins, leading to protection from new infections. mRNA vaccines are generally safer due to the fact that there are no live components of the disease, however the mRNA strand in the vaccine might cause an unintended immune reaction. 

(Sources: Centers for Disease Control and Prevention, World Health Organization, The Global Alliance for Vaccines and Immunizations)

What vaccines are currently available in the USA?

To date, there are 3 approved vaccines available for the prevention of COVID-19 in the USA that are recommended and authorized by the CDC. All the current vaccines are considered safe, effective and reduce the risk of severe illness.

The Pfizer-BioNTech vaccine is an mRNA vaccine, administered to individuals above the age of 16, and requires two shots that are 21 days apart. This vaccine is not recommended to those that have severe or immediate allergic reactions. However, it is proven to be safe and effective on those with known medical conditions associated with an increased risk of severe diseases such as hypertension and diabetes, as well as chronic illnesses that are controlled. The individual is considered fully vaccinated 2 weeks after the second dose. This vaccine is proven to have 95% efficacy in preventing COVID-19 symptomatic diseases when compared to a placebo. There are strict storage measures however, as this vaccine must be stored in an ultra-cold temperature-controlled unit, at -94 degrees Fahrenheit.

The Moderna vaccine is also an mRNA vaccine, recommended for people 18 years old and above. It requires two doses that should be approximately 28 days to 1 month apart. Similar to the Pfizer vaccine, if the individual has severe or immediate allergic reactions, it is not recommended for them to take this vaccine. However, there are various other types of COVID-19 vaccines available if the person falls in this category. The individual is considered fully vaccinated 2 weeks after the second shot. This vaccine is also safe for individuals that have underlying medical conditions and chronic illnesses. It has a very high efficacy (94.1%), however the main difference between the Moderna and Pfizer vaccine is that the Moderna vaccine may be stored for longer periods of time in a standard freezer and lasts 30 days under normal refrigeration.

The Johnson & Johnson’s Janssen vaccine is a viral vector vaccine, which only requires one dose. It is given intramuscularly and is available to individuals above the age of 18. If the person has a severe or immediate allergic reaction to any ingredient in the vaccine, it is recommended for them to abstain from this vaccine. Considering it is a viral vector vaccine, it carries a genetic code to the body’s cells to make the SARS CoV-2 spike proteins. The Johnson & Johnson Janssen vaccine was 66.3% effective in clinical trials at preventing laboratory-confirmed COVID-19 illness in people who had no evidence of prior infection 2 weeks after receiving the vaccine. People had the most protection 2 weeks after getting vaccinated.

(Source: Center for Disease Control and Prevention, U.S. Food and Drug Administration, Pfizer, World Health Organization)

What vaccines are currently approved in other countries?

This vaccine is a non-replicating viral vector vaccine that requires two doses given 8 to 12 weeks apart. It is administered in the United Kingdom and in over 165 countries such as Argentina, India, Brazil, Mexico and Pakistan. It is injected intramuscularly and is given to individuals who are 18 years old and above. According to the WHO, this vaccine has an efficacy of 63% against symptomatic COVID-19 infection. Greater vaccine efficacy is observed when the span between the two doses is longer, usually within 8-12 weeks.  The Oxford/AstraZeneca vaccine is safe and effective at protecting people from the extremely serious risks of COVID-19, including death, hospitalization and severe disease.

Sputnik V Vaccine is a viral vector, two-part vaccine against SARS-CoV-2 virus developed in Russia. This vaccine is made up of two different viruses under the adenovirus family, which are modified to contain the gene for making the spike protein. Each adenovirus is given separately, one at each dose, in order to boost the vaccination effect. Upon vaccination, the body’s immune system recognizes spike proteins as foreign and hence there is an onset of an immune response. Therefore, if the vaccinated person comes in contact with COVID-19, the body will begin attacking the spike proteins found by killing the virus, preventing its entry into the body’s cells and destroying infected cells. The Sputnik V vaccine is under review in the EU and has not been approved by the FDA yet, but is approved in over 60 countries worldwide as of May 2021, such as Argentina, Mexico, Bolivia, Brazil and various countries in the Middle East and Africa.

Sinopharm is the first approved inactivated virus vaccine produced in China. Since it uses an inactivated form of the pathogen that causes COVID-19, the killed virus is still immunogenic but it cannot replicate or infect cells; it only triggers an immune response. More than 45 countries have already approved their use and recently, WHO listed the Sinopharm COVID-19 vaccine for emergency use, giving the green light for this vaccine to be rolled out globally. It is mainly given to individuals above the age of 18. According to the antibody durability studied during clinical trials, this vaccine showed high levels of antibodies after 6 months of vaccination. Around 10 million doses have been administered and there have been no reports of severe reactions from the vaccination itself. Sinopharm announced that the vaccine was proven to be 79% effective against COVID-19.

Sinovac/CoronaVac vaccine is also an inactivated virus vaccine produced in China for the prevention of COVID-19, which was approved for emergency use in July 2020. It requires two doses that are administered 2 weeks apart and is given to individuals above the age of 18. Similar to the Sinopharm vaccine, it utilizes the killed viral particles from the SARS-CoV-2 virus to expose the body to foreign antigens, which trigger the immune response without causing the actual virus.  It is currently approved in several countries including China, Turkey, Brazil, Egypt and Thailand and recently, WHO listed the Sinovac/CoronaVac vaccine for emergency use. 260 million doses have been distributed to domestic and overseas markets. In a phase 3 clinical trial conducted in Brazil, the Sinovac/CoronaVac vaccine had an overall efficacy of 50.7% and appeared to be 48.9% efficacious amongst participants with underlying medical conditions. Additionally, in phase 3 clinical trial conducted in Chile, this vaccine was 67% effective in preventing symptomatic COVID-19 14 days after the second dose, and was 80% effective in preventing death.

Comirnaty is an mRNA vaccine with instructions for producing a protein from SARS-CoV-2, approved by the European Medicines Agency (EMA). It requires two doses given 3 weeks apart and can be administered to individuals aged 16 and above. In a trial consisting of 36,000 people, the vaccine showed 95% efficacy in preventing symptomatic COVID-19 cases and in protecting those at risk of developing severe symptoms. Most side effects are mild to moderate in severity and are gone within a few days.

(Source: European Medicines Agency, World Health Organization, Sinopharm, The Global Alliance for Vaccines and Immunizations, Frontiers in Immunology Journal, Nature and Springer Nature)

Side effects of COVID-19 vaccines

Common side effects on the injected arm may be experienced after 1 to 2 days upon vaccination. Some include arm soreness, redness and swelling. However, throughout the rest of the body, individuals may experience tiredness, headache, muscle and joint aches, chills, fever and nausea. The common side effects such as low-grade fever and muscle aches are signs that the body is responding to the vaccine, as they are the normal immune response towards the antigen. Side effects are more common and intense after the second dose of the vaccine. These symptoms are expected to be relieved in a few days. Taking painkillers prior to taking the vaccine to prevent side effects is not recommended due to the fact that its interference with the vaccine is not known. After vaccination however, the individual may take painkillers if they develop side effects.

Some of the rare side effects that may be experienced include thrombus (blood clots) and anaphylaxis. Anaphylaxis is when severe allergic reactions occur, however they can be treated immediately and effectively through medication. This side effect occurred in approximately 5 per million vaccinated with the Pfizer vaccine and 2.8 per million vaccinated with the Moderna vaccine. It is experienced usually within 30 minutes, hence why vaccinated individuals remain under observation for 15-30 minutes.

Due to rare adverse effects, many countries temporarily suspended the administration of particular COVID-19 vaccines such as those produced by AstraZeneca and Johnson & Johnson’s Janssen. According to  regulatory entities, the risk of developing thrombosis after vaccination with AstraZeneca is 1.1/100,000 for people aged between 20 to 29 years old, and the risk decreases to 0.2/100,000 in those aged between 60 to 69 years old. This rare side effect was also experienced upon vaccination with the Janssen vaccine but with less incidence. All of the cases occurred in mostly women under the age of 60, and it happened within 3 weeks of vaccination. Despite this, the CDC, FDA, and EMA stated that the benefits of the vaccines outweigh the risks considering how unlikely these side effects are.

(Source: World Health Organization, Center for Disease Control and Prevention, The Global Alliance for Vaccines and Immunizations, European Medicines Agency, BMJ Journal)

The impact of COVID-19 variants on vaccine efficacy

Variants occur when the virus begins to mutate, which is often caused by the increased opportunity a virus has to spread. The more a virus replicates, the more changes it may undergo. Most viral mutations do not influence the virus’s ability to cause infection, however depending on where the genetic material change occurs, certain properties such as mode of transmission or severity may be altered. The vaccines currently being administered have all been proven to provide protection against variants as they elicit a broad immune response that involves a large range of antibodies and cells. However, early studies have proven that some vaccines are less effective against certain variants.

 (Source: World Health Organization, Center for Disease Control and Prevention)

COVID-19 vaccine safety

All the approved vaccines have been rigorously tested and are continuously monitored. The vaccines mentioned met the FDA’s scientific standards for safety, effectiveness, and manufacturing quality, which are necessary to support emergency use authorization (EUA). The vaccines have shown a high level of efficacy in all populations and are proven to be safe and effective on people with various underlying medical conditions that are associated with risk of developing severe symptoms of COVID-19. Individuals who fall in the category of being immunocompromised, older in age with severe frailty, have a history of severe allergic reactions, have HIV, or are pregnant or breastfeeding should consult their doctor prior to taking the vaccine. Adverse side effects are very rare.   

(Source: World Health Organization, Center for Disease Control and Prevention, U.S. Food and Drug Association)

What to do after being fully vaccinated?

It takes time for the body to build the necessary protection and immunological memory after the vaccine. Hence, it is possible for a person to be infected with COVID-19 just before or after the vaccine if the necessary elapsed time to build immunity did not surpass. Additionally, the vaccines available are proven to prevent serious illness and death, yet the extent to which they prevent infection permanently remains unclear.

Even if the individual is fully vaccinated, the following precautions are necessary in public places (planes, buses, trains, and other forms of public transportation traveling into, within, or out of the United States):

  • Wearing a mask
  • Staying 6 feet apart from others
  • Covering the mouth when coughing or sneezing
  • Avoiding crowds
  • Hand washing

However, what can be done after being fully vaccinated includes:

  • Gather indoors with fully vaccinated people or unvaccinated people from a single household without wearing masks but staying 6 feet apart, unless some individuals are at increased risk of severe illness from COVID.
  • The person can gather and conduct activities outdoor without a mask, but should still avoid crowds.
  • If the person travels in the United States, they do not need to get tested before or after the trip or self-quarantine upon arrival.

(Source: Center for Disease Control and Prevention)

COVID-19 vaccine research and development

Worldwide, there are currently 92 COVID-19 candidates in the clinical trial process and 184 candidates in pre-clinical trials. NovaVax is a US protein subunit vaccine currently under development in phase 3 of clinical trials. Using recombinant nanoparticle technology, antigens from the COVID-19 spike proteins are generated. Based on testing and clinical trials, it was proven to be efficacious against severe and non-severe COVID-19, and appeared to be highly immunogenic due to the presence of spike-protein specific antibodies that prevent the spike proteins found on SARS-CoV-2 to bind to the host cell. In a UK phase 3 trial, it demonstrated 96.4% efficacy against the original strain of COVID-19, and 89.7% overall. In South Africa, the efficacy was reported to be 50%, however it was hypothesized that this was due to the dominance of the COVID-19 variant which may not react as effectively to the antibodies stimulated by the vaccine. Nevertheless, in both cases, it was 100% effective in preventing severe cases of COVID-19.

Another vaccine currently in phase 3 of clinical trials that is under review by the EMA is CureVac. This German developed vaccine uses a natural, unmodified mRNA technology to instruct the human body to activate the immune system through instructions to produce the spike proteins. The mRNA is encapsulated, meaning it is contained in lipids to prevent the mRNA from being broken down quickly and improve mRNA delivery. Based on the phase 3 trials, it was proven to have humoral immunogenicity and efficacy against severe and non-severe COVID-19.

The CanSino Biologics Inc. vaccine, currently being developed by the Beijing Institute of Biotechnology, is also in phase 3. It uses a harmless, non-replicating viral vector, known as Adenovirus type 5, to carry the antigens of the SARS-CoV-2 virus to the human cells. The company previously used this same method for developing a vaccine for Ebola. It proved to be efficacious against severe and non-severe COVID-19 based on limited results from a single dose phase 3 trial, in which it proved to have 65.7% efficiency in preventing symptomatic cases and 91% in preventing severe disease. Additionally, it was approved for use by the Chinese military and phase 3 trials are being conducted in Saudi Arabia, Pakistan and Russia. 

Covaxin is the first indigenous vaccine in India, developed by Bharat Biotech. It uses an inactivated virus as they do not replicate and hence this diminishes the pathological effects. It requires two doses, which should be given 28 days apart. India’s first and largest efficacy phase 3 trial is currently being conducted for this vaccine, including 25,800 participants. The results from the interim trial demonstrated that the vaccine has 81% efficacy after the second dose. The current data proves it is effective against the UK variant strain as it induced antibodies that can neutralize such variant.

Soberana 02 is the first Latin American vaccine to advance to phase 3 of clinical trials. It is under development by the Instituto Finlay De Vacunas in Cuba. It is a protein subunit vaccine and requires two doses administered within 14 days apart. This protein subunit vaccine is based on a portion of the spike protein that binds to the human cells receptor, inducing the generation of neutralizing antibodies. Hence, upon infection with COVID-19, the binding process is blocked. This vaccine is unique as it is the only existing “conjugate vaccine” for COVID-19, since it combines the antigen’s receptor binding domain with a deactivated form of tetanus to boost the immune response. It was proven to be efficacious against severe and non-severe COVID-19 and successfully caused humoral immunogenicity. The exact efficacy data is still unknown yet, and is expected to be available by June. It is currently being administered in Havana and Abdala in Santiago de Cuba and Guantanamo.

(Source: The Global Alliance for Vaccines and immunization, NovaVax, Curevax, European Medicines Agency, World Health Organization, Bharat Biotech, JCI Insight Journal, LSE Journal)

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