Vaccines

A vaccine is a weakened or killed pathogen or part of a pathogen that, when injected into the body, stimulates antibody production (Vaccines, 2020). This results in a primary response to the epitopes of the modified immunogen and generates immunity by inducing the production of a large amount of B and T memory cells (Mak, 2014). Vaccination is therefore the clinical application of immunisation, designed to artificially help the body defend itself against a pathogenic threat (Vaccines, 2020).

The first ever vaccine produced was made by Louise Pasteur to combat Anthrax (Vaccines, 2020). He realized that by heating a weakened form of the anthrax he could reduce it’s pathogenicity (Vaccines, 2020). He then administered this weakened, heated pathogen into a group of sheep. The sheep’s immune system then seemed to recognize the anthrax bacteria and produce antibodies against it (Vaccines, 2020). Pasteur then infected both this vaccinated group of sheep and an unvaccinated group of sheep with anthrax. All the vaccinated sheep survived and every unvaccinated sheep died (Vaccines, 2020).

Pasteur led the way for a new era in medicine, that of preventative medicine. Robert Koch, a renowned researcher in the 1800s, realized the importance of vaccination but stated that there should be guidelines to the where the focus on immunization should be (Vaccines, 2020). He thus came up with criteria for vaccine development and these are known now as Koch’s postulates, they include the following:

· The agent must be present in every case of the disease

· The agent must be isolated from the host and grown in a lab dish

· The disease must be reproduced when a pure culture is inoculated into a healthy susceptible host

· The same agent must be recovered again from the experimentally infected host (Vaccines, 2020).

As the era of vaccinations developed, so did the way the vaccines were produced, leading to a variety of types of vaccines. The first and most publically misunderstood vaccine is the live vaccine. This form of vaccination uses a weakened (attenuated) form of the virus, i.e. not directly injecting an actively disease-causing pathogen into the body (Pokhrel, 2020). Live vaccines are used for measles, mumps, rubella, and varicella viruses (Pokhrel, 2020). The advantages of using live vaccines are that they provide for a lifelong immunity with only one or two doses (PublicHealth.org, 2020). The problem with these live vaccines is that they are contraindicated in individuals with weakened immune system, such as in HIV/AIDS patients and cancer patients (PublicHealth.org, 2020). This is due the risk that the weakened virus becomes stronger and causes disease (PublicHealth.org, 2020).

The contraindications of live vaccines led to the development of killed (inactivated) vaccines, toxoid vaccines, and biosynthetic vaccines. The killed vaccines are made from proteins or other small pieces (such as carbohydrates) taken from a virus or bacteria, making them safer than live vaccines for the immunocompromised (Pokhrel, 2020). The downside is that many doses of the vaccine are needed in order to develop an adequate immune response (PublicHealth.org, 2020). A toxoid vaccine contains a toxin or chemical made by the bacteria or virus and makes the vaccinee immune to the harmful effects of the disease rather than the infection itself (Pokhrel, 2020). The last type of vaccine is the biosynthetic vaccine. This contains man-made substances that are very similar to a piece of bacteria or virus, misleading the body into thinking it has a viral/bacterial infection (Pokhrel, 2020).

Vaccine development has evolved into a strict and well-governed process consisting of 6 stages:

· Stage 1: Exploratory stage

o This stage is supposed to last 2 - 4 years and is aimed on research and data collection (CDC, 2020; Offit, 2018).

· Stage 2: Preclinical stage

o This stage consists of cell culture or tissue culture systems and includes anima testing (mice or monkeys) (CDC, 2020; Offit, 2018). The aim of this stage is to test the safety of the vaccine and its immunogenicity (Offit, 2018). It also gives an indication of the safest starting dose in humans and gives an idea of the safest method of administration (Offit, 2018). This stage lasts 1 – 2 years and is the stage that most vaccine candidates never surpass due to inefficient immunogenicity (Offit, 2018).

· Stage 3: Clinical stage

o This stage occurs after an Investigational New Drug (IND) application has been submitted and approved by the Food and Drug Safety Administration (FDA) (Offit, 2018). Once approval has been granted, the 3 phases of this stage can begin. The first phase is the small groups phase, consisting of 20 – 80 people with the goal being to assess the safety of the vaccine (CDC, 2020). The second phase is expanding the number of people by giving the vaccine to all those at high risk of the disease that is trying to be prevented (CDC, 2020). The goal in the second phase is to assess safety, immunogenicity, proposed doses, schedule and method of administration (CDC, 2020). The final phase is distributing the vaccine to thousands of people.

· Stage 4: Regulatory overview and approval

o This is the responsibility of the FDA and is a multistep, complex approval process (CDC, 2020).

· Stage 5: Manufacturing

· Stage 6: Quality control

The steps in vaccine development are important to enforce quality control and safety before human administration. This field of immunology is quickly expanding and preventative therapies against viruses and bacteria will remain an important topic for many researchers.

References

Allan, A., 2020. Why The Push For A Quick Coronavirus Vaccine Could Backfire. [online] POLITICO. Available at: <https://www.politico.com/news/2020/03/20/why-the-push-for-a-quick-coronavirus-vaccine-could-backfire-139854> [Accessed 2 April 2020].

Ahmed, I., 2020. US Just Started The First Human Trial Of A Vaccine For The New Coronavirus. [online] ScienceAlert. Available at: <https://www.sciencealert.com/us-begins-first-human-trial-of-coronavirus-vaccine> [Accessed 27 March 2020].

Cdc.gov. 2020. Vaccine Testing And Approval Process | CDC. [online] Available at: <https://www.cdc.gov/vaccines/basics/test-approve.html> [Accessed 26 March 2020].

Garde, D., 2020. An Updated Guide To The Coronavirus Drugs And Vaccines In Development. [online] STAT. Available at: <https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/> [Accessed 27 March 2020].

Mak, T., 2014. Primer To The Immune Response. 2nd ed. Elsevier, p.Chapter 14.

Offit, P., 2018. Vaccine Development, Testing, And Regulation. [online] Historyofvaccines.org. Available at: <https://www.historyofvaccines.org/content/articles/vaccine-development-testing-and-regulation> [Accessed 27 March 2020].

Pokhrel, P., 2020. Differences Between Primary And Secondary Immune Response. [online] Microbiology Notes. Available at: <https://microbiologynotes.com/differences-between-primary-and-secondary-immune-response/> [Accessed 26 March 2020].

PublicHealth.org. 2020. How Vaccines Work | Publichealth.Org. [online] Available at: <https://www.publichealth.org/public-awareness/understanding-vaccines/vaccines-work/> [Accessed 26 March 2020].

Schreiber, M., 2020. The Risky Race For A Quick Coronavirus Vaccine. [online] The New Republic. Available at: <https://newrepublic.com/article/156932/risky-race-quick-coronavirus-vaccine> [Accessed 2 April 2020].

Writer, N., 2020. Researchers Fast-Track Coronavirus Vaccine By Skipping Key Animal Testing First. [online] livescience.com. Available at: <https://www.livescience.com/coronavirus-vaccine-trial-no-animal-testing.html> [Accessed 27 March 2020].

4t<https://www.ncbi.nlm.nih.gov/books/NBK24653/> [Accessed 26 March 2020].