By Yuchen Lin
We will have received several vaccines throughout our life, but why do we need them? How do they protect us? A vaccine is a type of medicine that can train our immune system to defend us against diseases never encountered before. In other words, a vaccine is used to prevent instead of treat diseases. So far, vaccines have successfully eradicated deadly diseases including smallpox and almost eliminated poliovirus, meningitis and measles. Under the current pandemic, COVID-19 vaccines have helped protect people against symptomatic infection and reduce illness worldwide.
Vaccines can protect us against infections including viruses, bacteria, and parasites. To achieve this, vaccines introduce weakened or inactive harmless pathogen molecules, known as antigens, into our bodies to trigger immune responses. Vaccines also contain certain amounts of preservatives and stabilisers, sorbitol and citric acid that are readily found within the body or in food. The most abundant ingredient is water. Some vaccines also have aluminium hydroxide to strengthen and prolong the immune response they trigger.1 The injected antigens do not cause diseases in people receiving the vaccine but promote the immune system to safely learn to recognize these invaders, produce antibodies against them, and store memory. When we are infected by the real pathogen in the future, our immune system can recognize and attack it immediately before it spreads and causes severe illness. Rather than containing the antigen, some new vaccine types can trigger antigen production inside our body and train the immune system in the same way. Most vaccines allow the production of long-lived antibodies or the development of memory cells to give lifelong protection.
One advantage of vaccination is herd immunity. A devastating infectious disease can be eliminated without vaccinating every individual. Once enough people have been vaccinated against a pathogen, the chance of disease outbreak will be largely reduced because the pathogen does not have enough hosts to establish, replicate and spread, having difficulty circulating.2 Thus, it benefits people who are not immunised. Some vaccines are unsuitable for individuals, such as infants, the elderly, pregnant women, and people with compromised immune systems as vaccines might trigger severe allergic reactions or other negative consequences. Therefore, herd immunity renders protection for these people if they live in a community where most people are vaccinated.3 The more people being vaccinated, the less likely for them to be at risk.
In general, there are four categories of vaccines: whole organism vaccines, subunit vaccines, nucleic acid vaccines, and viral vector vaccines. There are two types of whole-organism vaccines that traditional vaccines are based on. One is the live-attenuated vaccines in which a weaker or asymptomatic form of the pathogen will be introduced to elicit immune responses. These vaccines are excellent in stimulating the immune system for lifelong immunity but must be precisely controlled to provide a desirable level of immunity. Examples include the measles, mumps, and varicella vaccines we had at a young age. However, such vaccines are dangerous for people with compromised immune systems as weakened pathogens may get stronger and evade their immune systems to cause the same illness as a real infection.
Another is the inactivated vaccines in which pathogens are killed by heat or chemicals, and then the dead cells are introduced into the body. Vaccines for polio, hepatitis A, and rabies contain such inactivated pathogens. These vaccines can be freeze-dried and stored easily, and they are safer than live-attenuated vaccines because they avoid the risk of pathogens reverting into full virulence form.4 But they have limitations on the mode of presentation and the immune responses they trigger, making them less potent with a shorter duration than live-attenuated vaccines. Therefore, multiple doses or booster shots are usually required within a few weeks or months interval for enhancing efficacy.
Traditional inactivated influenza vaccines (IIV) have been gradually replaced by live-attenuated influenza vaccines (LAIV). IIV activates the immune system to produce strain-specific short-lived antibodies, but LAIV, the intranasally administered vaccine, can elicit immune responses that resemble consequences of natural influenza and provide broader clinical protection in children.5 Protective antibodies are produced locally and systemically, and immune responses involve humoral and cellular compartments. Because influenza viruses often mutate and escape immune defence, the vaccines must be updated annually.5 The ability of LAIV in triggering long-term immunological responses is promising for developing the universal influenza vaccine without needing annual doses.
Subunit vaccines are developed by isolating specific proteins or carbohydrates from the pathogen. Similarly, when these subunits are injected into the body, they activate immune responses without provoking illness. They reduce the possibility of adverse effects because only part of the pathogen is injected. However, adjuvants are often required as their elicited immune responses are weaker.
Nucleic acid vaccines are promising alternatives to conventional vaccines. They deliver genetic transcripts that encode selected protein antigens from pathogens. The transcript instructs our cells to translate the viral proteins inside our body. Our immune system identifies the proteins and responds like a natural defence against infection. Because the antigen is produced inside our own body in large quantities, the immune reaction is strong and efficient.
Viral vector vaccines are similar to nucleic acid vaccines in introducing pathogenic DNA into the body to trigger antigen production and train the immune system to combat. The difference is that a harmless virus is used here as the vector. Usually, adenovirus is edited to contain the DNA and injected to hijack cellular machinery.
Although no nucleic acid or viral vector vaccines have been licensed for human use, they combine the positive aspects of both live-attenuated and subunit vaccines and demonstrate safe implications in clinical trials.6 Currently used COVID-19 vaccines produced by Pfizer and Moderna are mRNA vaccines that encode viral spike protein. Because of its power in eliciting strong immune reactions, some people develop symptoms like fever after vaccination as an indication of immune defence.
A DNA vaccine, ZyCoV-D vaccine, against SARS-CoV-2 was developed and approved for emergency use in India.7 After injection, the genetic material encoding spike protein is translocated to the host cell nucleus, where the promoter encoded in the vector structure is activated, leading to transcription and translation of the viral genome. Viral proteins or protein fragments will be further processed into peptides that bind to MHC class I or II on antigen-presenting cells. Different cells use different MHC classes to present the antigen to activate naïve T cells. Predominantly, CD8+T cell immunity stimulates the release of cytokines (IFNγ) and tumour necrosis factor α. Hence, macrophages are activated to support the cell-mediated immune response. CD4+ helper T cells are activated, as well as naïve B cells, resulting in antibody production as a humoral immune response.8 DNA vaccine has been of great interest not only due to its ability to elicit humoral and cellular immune responses but also its large-scale, low-cost production and high stability. Its convenient storage condition, -2-8°C, makes it highly practical. Clinical trial results showed 67% protection against symptomatic COVID-19, making it a potent strategy.
Although no vaccine can provide 100% protection against any disease and herd immunity does not give complete protection for people who cannot be vaccinated, substantial protection is formed to diminish the risk of developing severe symptoms. Therefore, getting vaccinated helps to protect you and the people around you.
1. British Society for immunology. How vaccines work. https://www.immunology.org/celebrate-vaccines/public-engagement/guide-childhood-vaccinations/how-vaccines-work. [Accessed 23rd Nov 2021]
2. World Health Organisation. How do vaccines work? https://www.who.int/news-room/feature-stories/detail/how-do-vaccines-work. [Accessed 23rd Nov 2021]
3. European Commission. How do vaccines work? https://ec.europa.eu/info/live-work-travel-eu/coronavirus-response/safe-covid-19-vaccines-europeans/how-do-vaccines-work_en. [Accessed 23rd Nov 2021]
4. Francis, M.J. (2017) Recent Advances in Vaccine Technologies. Vet Clin North Am Small Anim Pract. 48(2): 231-241. Doi: 10.1016/j.cvsm.2017.10.002
5. Mohn, K.G. et al., (2018) Immune responses after live attenuated influenza vaccination. Hum Vaccin Immunother. 14(3): 571-578. Doi: 10.1080/21645515.2017.1377376.
6. Deering, R.P. et al., (2014) Nucleic acid vaccines: prospects for non-viral delivery of mRNA vaccines. Expert Opin Drug Deliv. 11(6): 885-99. Doi: 10.1517/17425247.2014.901308.
7. Nature. India’s DNA COVID vaccine is a world first – more are coming. https://www.nature.com/articles/d41586-021-02385-x. [Accessed 24th Nov 2021]
8. Silveira M.M. et al., (2021) DNA vaccines against COVID-19: Perspectives and Challenges. Life Sci. 267: 118919. Doi: 10.1016/j.lfs.2020.118919.