Vaccines are one of the greatest achievements in medicine due to their ability to prevent millions of infections and save many lives each year. Thanks to vaccines, certain diseases, such as smallpox, have been completely eradicated while others, such as polio, have seen a drastic decline in cases. Recently, vaccinations have taken the spotlight in the media as we continue to search for a COVID-19 vaccine. In order to understand the ongoing work with this new vaccine, we must first take a look at the different types of vaccines which are available today. 

Live-attenuated vaccines

Live-attenuated vaccinations are extremely effective at preventing disease through their ability to mimic natural infection and create a long-lasting immune response. These vaccines work by introducing a weakened form of the germ that causes the disease, so as to induce immunity without causing serious illness. Still, individuals with weakened immune systems may not be suitable candidates for vaccination due to the risk of introducing even the weakened form of the live virus. Examples of live-attenuated vaccinations include measles, mumps, and rubella (MMR), rotavirus, smallpox, chickenpox, and yellow fever.

Inactivated vaccines

Inactivated viruses work by using the killed form of the germ that causes disease. Since it is using the killed version, inactivated vaccines do not provide as strong of protection as live-attenuated vaccines. This is the reason for booster shots as it is a way for an individual to maintain ongoing immunity against the disease. With most inactivated vaccines, adjuvants, such as aluminum salts, are also used in order to help strengthen and lengthen the immune response to the vaccine. Due to this, more local reactions, such as a sore arm, may be noted following inactivated vaccine administration. Common types of inactivated vaccines include vaccines for hepatitis A, flu, polio, and rabies.

Subunit, recombinant, polysaccharide, and conjugate vaccines

These types of vaccines contain only pieces of the pathogen which they are working to protect against. Pieces may include isolated proteins, sugars, or capsid, which is the casing around the germ. As these vaccines are only using specific pieces of the germ, they provide a very strong and targeted immune response against the pathogen. They are also safe for individuals with weakened immune systems to receive as they do not convey any risk of introducing the live virus. As with inactivated vaccines, individuals may also require booster shots in order to maintain immunity. Common diseases that these vaccines are used to protect against include hepatitis B, HPV, whooping cough, pneumococcal disease, meningococcal disease, shingles, and hib disease. 

Toxoid vaccines

Some bacterial diseases are known to be caused by a toxin produced by the bacterium rather than by the bacterium itself. Toxoid vaccines then work by inducing immunity to the harmful products made by the germ rather than the germ itself. Therefore, the immune response is targeted toward the toxin instead of the whole germ. This type of vaccination also falls under the category of an inactivated vaccine, except in this scenario the agent is an inactivated toxin, not an inactivated form of the bacteria.Toxoid vaccines also require booster shots to maintain immunity and are typically used to protect against diseases such as diphtheria and tetanus. 

mRNA vaccines

Despite the success of the vaccines mentioned above, there remain challenges in creating vaccines which are able to successfully fight against a variety of infectious pathogens, especially pathogens which are better able to evade the adaptive immune response. Current research suggests that mRNA vaccines have the potential to solve challenges in vaccine development for both infectious disease and cancer. So what is mRNA?

mRNA molecules are made by our bodies by using DNA as the template. mRNA is then translated in order to build proteins that the body needs. These vaccines work by introducing an mRNA sequence which is coded to produce the disease specific antigen. An antigen is any foreign substance which causes the body to produce antibodies which can then mount an attack against the antigen. Therefore, once the mRNA is introduced into the body, your body’s cells use that genetic material to produce the antigen which then becomes displayed on the cell’s surface. At this point, the antigen becomes recognized by the immune system. This process helps the body to prepare to fight the real antigen, should it be encountered at a later point. mRNA vaccines are not only inexpensive to produce, but they are also safer for patients as they are not produced with infectious elements. 

Viral Vector Vaccines

Viral vector vaccines use live viruses in order to transmit DNA into our cells. Like a live-attenuated virus, viral vector vaccines have the potential to actively invade host cells and replicate. As such, viral vector vaccines generally consist of a live-attenuated vaccine that has been genetically engineered to carry DNA that encodes for antigens. These antigens can then elicit an immune response after they become expressed by the infected cells. For instance, in the case of COVID-19 a viral vector vaccine will use a virus in order to deliver specific coronavirus genes, which encode for antigens, into cells and provoke an immune response without causing infection.

The COVID-19 vaccine

One of the goals for the COVID-19 vaccine is to provide long term protection so as to avoid re-infection. It is hoped that the vaccine will be able to be received by a large number of the population so as to provide adequate protection. As such, it is important that the vaccine is safe for many individuals to receive. Vaccines which pose less risk of causing infection due to introducing the live virus are then preferred so that older individuals or individuals with comorbidities may still have access to the vaccine. These stipulations make inactivated, subunit, recombinant, polysaccharide, conjugate, and mRNA vaccines the best options for a COVID-19 vaccine. At the moment, there are over 135 vaccines in pre-clinical trials, 18 vaccines in phase I trials testing safety and dosage, 12 vaccines in phase II trials which are expanded safety trials, 7 vaccines in phase III large-scale efficacy tests, and 1 vaccine approved for limited use. The F.D.A has announced in June that in order for a COVID-19 vaccine to be considered effective, it would need to provide protection in at least 50% of vaccinated individuals. 

A recent study was published in the New England Journal of Medicine on July 14th, 2020 which discussed preliminary findings for a candidate vaccine made by Moderna. Many of the current endeavors to develop a vaccine for COVID-19 have involved the use of an mRNA vaccine. Like other mRNA vaccines, this vaccine works by introducing an mRNA molecule which then produces an antigen. In the case of this COVID-19 vaccine, the antigen produced is the SARS-CoV-2 spike (S) glycoprotein, or the S glycoprotein. Coronaviruses have spike-like structures on their surfaces, which is made up by this S glycoprotein. When infection with COVID-19 does occur, the S glycoprotein is responsible for mediating viral entry by allowing attachment to the host cells. Therefore, the vaccine will effectively target the protein which allows viral entry so that the virus is no longer able to infect and reproduce in host cells. Many of the other candidate vaccines for COVID-19 also target this specific protein as well. Initial findings have shown promising results with the vaccine being both safe and effective. Phase 3 trials will begin in the summer of 2020.

Pfizer, in accordance with BioNTech and Fosun Pharma, have also developed an mRNA vaccine which targets the S glycoprotein. On July 27th they began their combined phase II/III trial with over 30,000 volunteers in the US, Argentina, Brazil, and Germany. Pfizer was recently given a $1.9 billion contract from the Trump administration to deliver 100 million doses by December. If their candidate vaccine does receive approval, Pfizer expects to manufacture over 1.3 million doses of the vaccine for worldwide use by the end of 2021. CanSino Biologics, a company based in China, has recently gained limited approval for their candidate viral vector vaccine which uses an adenovirus to deliver coronavirus genes encoding for the S glycoprotein antigen. This vaccine was approved by the Chinese military for one year as a specially needed drug, however it’s still to be determined if the vaccine will be mandatory or optional for soldiers. Other candidate vaccines include inactivated vaccines and subunit vaccines. Realistically, it will take around 12-18 months for a vaccine to be developed and tested in human clinical trials. It is important to take this time in order to ensure the safety and efficacy of the vaccine before introducing it to the population at large. Once a vaccine does finally reach approval, it will take time to produce, distribute, and administer on a global scale. It is likely that two vaccinations will be required in order to gain immunity, which will start to appear one to two weeks after the second vaccination. In the meantime, it is important to continue to maintain social distancing and to wear a mask while in public spaces.