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Blog COVID-19 Guest Blog

The COVID-19 Vaccine Landscape

Written by Miguel Leon Rios
Read about Miguel’s research here:
https://news.liverpool.ac.uk/2019/05/15/becoming-an-expert-investigating-vaccines-against-viral-stomach-bugs/

The COVID-19 Vaccine Landscape

The global COVID-19 pandemic picture is still unclear as the novel coronavirus outbreak shifts constantly around the world. While the number of cases rise critically in South America’s first wave, the UK and European countries have begun to lift their lockdown measures amidst this COVID-19 pandemic. At the same time, South Korea and China, where coronavirus cases seemed to have disappeared, have seen a second wave of infections. However, a common question emerges among this COVID-19 rollercoaster: Will we have a vaccine soon? 

A matter of time 

Timing is crucial in vaccine research. More than five months have passed since the genetic sequence of SARS- CoV-2, the virus that causes COVID-19, which was published on 11th January 2020. This discovery sparked an unprecedented global research effort to develop a vaccine against this disease1, involving next-generation technology platforms and novel approaches with a hope to speed up this process. However, vaccine development involves a multi-stage process of research and testing, which typically takes more than ten years to be completed2 (Fig. 1). Therefore, we must remain cautious in light of a new vaccine.

Fig. 1. Vaccine research and development. Adjusted from The Association of the British Pharmaceutical Industry (ABPI)

What is the current picture?

A recent overview of the global landscape of COVID-19 vaccines by the World Health Organisation (WHO) included more than 140 vaccine candidates from different research groups and developers around the world3. From those, 129 candidate vaccines are under preclinical evaluation, which means a preliminary laboratory exploration but not yet in human trials. On the other hand, 13 candidate vaccines have entered the clinical evaluation stage, which is a three-phase process involving human subjects (Fig. 2). 

Fig. 2. How a new vaccine is developed. Adjusted from The Journey of Your Child’s Vaccine. Centres for Disease Control and Prevention (CDC)

OK, but can we speed up this process?

In terms of vaccine research time we are progressing at super-fast speed in this scenario. Just consider that the first set of COVID-19 cases, a new type of viral pneumonia, were reported to WHO on 4th January 2020 (Fig.3). Two months later, the first COVID-19 vaccine entered first-in-human trials within record breaking time on 16th March 2020. Scientists and international organizations around the world are still racing to produce and deliver a safe and effective vaccine within an 18-month period1-3.

Fig. 3. Source: Word Health Organization (WHO) official twitter account.

So, do we have a vaccine yet? 

From the array of advanced COVID-19 candidates under clinical development, only one promising study has started their phase 3 trial in Brazil4 (Fig. 4). This a non-replicative viral vector vaccine developed by the University of Oxford and the British-Swedish company AstraZeneca5. As we previously described, this candidate works as an inactive vaccine by using a different non-live virus to deliver coronavirus genes into our cells. In other terms, it can´t reproduce itself but it can still provoke an immune response.

COVID-19 Vaccine Tracker
Fig. 4. Coronavirus Vaccine Tracker. Source: The New York Times.

Currently, this vaccine is also moving to Phase II/III in England and will hopefully deliver positive results by next year. A different approach has been employed by The Murdoch Children’s Research Institute in Australia. The experimental coronavirus vaccine, which is currently in phase 3 trial, utilises the Bacillus Calmette-Guerin vaccine6.  The BCG vaccine is made from a weakened strain of tuberculosis bacteria and been widely used since the 1920s to fight TB7.

Researchers expect to observe partial protection against SARS-COV-2 as observed for other diseases7,8.  Only data and results will decide if the remaining vaccine candidates could progress to phase 3 human trials and if this global effort could be translated into a successful vaccine by early 2021. 

References

  1. Usher AD. COVID-19 vaccines for all?. Lancet. 2020;395(10240):1822-1823. doi:10.1016/S0140-6736(20)31354-4
  2. Thanh Le T, Andreadakis Z, Kumar A, et al. The COVID-19 vaccine development landscape. Nat Rev Drug Discov. 2020;19(5):305-306. doi:10.1038/d41573-020-00073-5
  3. Draft landscape of COVID-19 candidate vaccines. WHO. 2020; June 22. [cited 2020 Jun 23]. Retrieved from https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines
  4. Corum.J, Grady. D and Zimmer. C. 2020. Coronavirus Vaccine Tracker. The New York Times. Available from: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  5. Current Controlled Trials. ISRCTN89951424. A phase III study to investigate a vaccine against COVID-19, [cited 2020 Jun 23]. Available from: https://doi.org/10.1186/ISRCTN89951424
  6. ClinicalTrials.gov. NCT04327206, BCG Vaccination to Protect Healthcare Workers Against COVID-19 (BRACE) [cited 2020 Jun 23]. Available from: https://clinicaltrials.gov/ct2/show/NCT04327206
  7. World Health Organization. BCG vaccine: WHO position paper, February 2018 Recommendations. Vaccine. 2018;36(24):3408-3410. doi:10.1016/j.vaccine.2018.03.009
  8. Caryn Rabin R. 2020, April 5. Can an Old Vaccine Stop the New Coronavirus?. The New York Times. Available from: https://nyti.ms/2JCcTxx 
Blog COVID-19

COVID-19: Let’s Talk Vaccines

Grab a coffee, lets do this!

Therapeutic options

We discussed the latest updates on drug therapies as countermeasures for COVID-19 here. Instead of treating diseases, vaccines have the capacity to prevent them.

No, really what is a vaccine and how do they work?

Like natural infections, vaccines work by initiating a first line immune response, known as the innate immune response. In turn this allows the body to remember the pathogen, preparing the body to defend itself on the pathogens next attack, known as an adaptive immune response 1. Each pathogen (or vaccine) contains unique and specific shapes that the body’s immune system is able to recognise. Once the pathogen is dealt with, the adaptive immune response establishes what we call immunological memory, which is essentially the main goal of vaccination 1.

There isn’t just one type of vaccine either, scientists have found different ways of getting your immune system ready and prepared for infectious diseases.  

Two main types of vaccines

Vaccines can be split into two main categories 2:

Live attenuated vaccines

This is when scientists take the causative agent of the disease, i.e. the virus or the bacteria and weaken it so it can no longer cause disease in healthy people. This is not an appropriate vaccination method for those with an immune system that does not work 1,2.

Live attenuated vaccines tend to be produced for viral diseases, as viruses have fewer genes and weakening these pathogens can be achieved more reliably 1.

Examples of Live Attenuated Vaccines used in the UK are as follows:

  • Rotavirus vaccine
  • Measles Mump and Rubella Vaccine
  • Chickenpox vaccine
  • And more….

If you are big on your travelling, you may have had the Yellow Fever Vaccine or the oral typhoid vaccination.

Inactivated vaccines

These types of vaccines contain either; the whole bacteria or virus that have been “killed”. OR, small elements of the disease-causing agents such as associated proteins or sugars. All of which cannot cause disease, even in those with severely weakened immune systems. The immune response produced by these vaccines aren’t always as powerful as those observed in a live attenuated vaccine, and because of this may require boosters 1,2.

Adjuvants are often added to inactivated vaccines to help boost the immune response and thus make them more protective.

Adjuvant… what?

So, an adjuvant is actually an aluminium salt that is added to vaccines to help produce an immune response, such as aluminium hydroxide, aluminium phosphate or potassium aluminium sulphate.

This is not like injecting an aluminium can into your body, by the way. Aluminium is actually a very natural metal found naturally in water, food and the earth itself. The amount used in vaccines is very tiny and is a vital element for these types of vaccines to protect you2.

“Whole killed” vaccines

Some examples of diseases prevented with inactivated “whole killed” vaccines are; poliovirus, hepatitis A, Rabies and Japanese Encephalitis 2.

Subunit vaccines

There are 3 types of subunit vaccines; toxoid, conjugate and recombinant vaccines. All of which essentially take a subunit of the pathogen and turn this into a vaccine 2. When scientists say subunit, they are referring to only a part, or an element of the pathogen as opposed to the whole thing.

Toxoid

Many bacteria release toxins during an infection. Our bodies are able to recognise these toxins and produce an immune response. Therefore, making these a good target for vaccines. Examples of toxoid vaccines are Diptheria, tetanus and pertussis (whooping cough) 2.

Conjugate

The work “conjugate” means connected or joined. Sometimes, the subunit of a pathogen doesn’t elicit a good enough immune response by itself, so the subunit is joined to something else. Quite often the subunit is joined to the tetanus or diphtheria toxoid. Examples of conjugate vaccines are Haemophilus influenzae B, Meningitis C, Pneumococcal and Meningococcal vaccines 2.

Recombinant vaccines

These types of vaccines take the genetic code (DNA) from the virus or bacteria that we want to protect ourselves from. In the case of the Hepatitis B vaccine, the DNA is inserted into yeast cells, which are able to produce surface proteins of the pathogen. This is then purified and used as the active part of the vaccine. Examples of recombinant vaccines: Hepatitis B, Human Papilloma Virus and Meningitis B vaccines 2.

Vaccine trials are essential

Like we discussed in our article about drugs, all medicines have to go through a robust clinical trial. This is to ensure that the vaccine is not only safe, but to test whether the vaccine works and provide sufficient protection.

Vaccines available

Phase I: a small-scale trial to assess whether the vaccine is safe in health people.

Phase II: more participants are recruited, and the study assess the efficacy of the vaccine, vaccine safety and the immune response is studied.

Phase III: The vaccine is studied under natural disease conditions, hundreds to thousands will be recruited to the study.

If the vaccine retains safety and works well over a defined period of time, the manufacturer of the vaccine is able to apply for a licence to market the product for human use.

Phase IV: The vaccine has been licensed and approved for use, however, data is still collected to monitor adverse effects and to determine the longevity and effectiveness of the vaccine 3,4.

Eradication of disease

In May 1980, the world was declared free of smallpox 5. The last naturally occurring case of this disease was observed in Somalia in 1977 5. Edward Jenner in 1796 observed that those who contracted cowpox, a disease known to be very mild, developed immunity against smallpox 6. This inspired Jenner to prepare a vaccine containing material from cowpox lesions, where he knew “the annihilation of smallpox must be the final result of this practice”. Despite this ground breaking discovery, it took nearly 200 years to eradicate smallpox 5. Smallpox remains the only human infection eradicated by vaccination.

Of course, it is not only humans that are vaccinated against infectious agents, but our pets and our livestock are also vaccinated. Rinderpest is known as the most devastating infectious disease of cattle, associated with a mortality rate more than 70% 7. Rinderpest is a virus belonging to the same virus family as measles. In 1918, the first vaccine was developed in Korea as an inactivated virus. This later got developed into a live attenuated vaccine until 1989 where the first recombinant rinderpest vaccine was developed 7. However, before the recombinant vaccine got to trial, eradication was achieved with the use of Plowright’s live attenuated vaccine 7.

Vaccines will allow us to prevent the disease, protect vulnerable members of our communities through herd immunity and in turn reduce the pressure on healthcare systems.

There is currently no vaccine for any of the known coronaviruses. Despite massive research efforts, it is not expected that a vaccine against SAR-CoV-2 will be available in less than 18 months 8. Keep an eye out for a break down on SARS-CoV-2 vaccines that are going through trial over the next couple of weeks.

References

1          Vetter, V., Denizer, G., Friedland, L. R., Krishnan, J. & Shapiro, M. Understanding modern-day vaccines: what you need to know. Annals of Medicine 50, 110-120, doi:10.1080/07853890.2017.1407035 (2018).

2          Group, O. V. Types of Vaccines, <https://vk.ovg.ox.ac.uk/vk/types-of-vaccine> (2020).

3          European Vaccine Initiative. Stages of Vaccine Development, <http://www.euvaccine.eu/vaccines-diseases/vaccines/stages-development> (

4          Stern, P. L. Key steps in vaccine development. Annals of Allergy, Asthma and Immunology (2020).

5          Strassburg, M. A. The global eradication of smallpox. American Journal of Infection Control (1982).

6          Jenner, E. History of the Inoculation of the Cow-Pox: Further Observations on the Variolae Vaccinae, or Cow-Pox. The Medical and Physical Journal (1799).

7          Yamanouchi, K. Scientific background to the global eradication of rinderpest. Veterinary Immunology and Immunopathology 148, 12-15, doi:https://doi.org/10.1016/j.vetimm.2012.06.006 (2012).

8          Grenfell, R., Drew, Trevor. Here’s why the WHO says a coronavirus vaccine is 18 months away, <https://theconversation.com/heres-why-the-who-says-a-coronavirus-vaccine-is-18-months-away-131213> (2020).

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