Vaccines have set the world back on the path to recovery from COVID-19. With increasing discussion on this crucial mechanism, this article seeks to answer some of the queries surrounding the COVID-19 vaccine.
How are vaccines developed?
Nowadays, vaccines are developed via different techniques. Four of these are explained below.
Inactive or weakened virus vaccine: This traditional method employs the killed, weakened, or fragments of the pathogen to induce an immune response in the body without the virus causing the disease. This is currently also the cheapest method (Krause et al, 2020).
The RNA vaccine: This method uses genetic molecules that encode the synthesis of a specific protein of the pathogen. In the case of COVID-19 and other diseases, the “spike protein” is used, which is present on the surface of the pathogen. When the body recognises this protein, it produces specific antibodies to neutralise it, promoting immunity to the disease. This method took decades to be developed, owing to several biotech-related obstacles and the high costs of research, materials, and storage, as RNA is fragile and has to be kept under cold conditions (below -30°C for some) (Jackson et al., 2020).
Non-replicant virus vector vaccine: This method uses a variant of the virus that cannot replicate even after infecting a person or fragments of the virus’ proteins (usually, the spike protein) to induce an immune response (WHO, 2021).
Protein subunit vaccines: This method also uses spike proteins. Because these are fragments of the virus, they are incapable of causing disease as they cannot infect host cells. As they are less likely to trigger a strong immune response, subunit vaccines often include a chemical agent called adjuvants designed to enhance immune responses (Medhi, 2020) (CEPI, 2020).
Vaccine efficacy and advancements
The pandemic has presented the perfect opportunity for challenges in vaccine development to be overcome. RNA vaccines have a higher efficacy than the traditional ones, but they are often more expensive, owing to the costly reagents and storage conditions required. Furthermore, most must be administered in two doses that are at set intervals apart. These are currently being used in Europe and the United States for COVID-19. Their widespread use could allow for major advances in the development of vaccines for other diseases such as cancer and multiple sclerosis (Jackson et al., 2020).
What do vaccine trials entail?
Vaccine production involves a series of steps, including regulations, laws, trials, and relevant infrastructure development. Several trials are needed to provide the active principle – namely, the component that should exert the desired effect of the drug. Following this, trials are undertaken to evaluate the vaccine’s efficacy and safety. In the pre-clinical phase, trials are conducted in vitro (known as “test-tube experiments”) and/or using animals (usually mice, rabbits, or monkeys) (Fiocruz, 2020).
Four test phases
During phase 1, the vaccine is tested on humans and security trials are performed. Phase 2 evaluates the efficacy of the vaccine and side effects, while phase 3 is concerned with efficiency, efficacy, and security trials with a larger group than in previous phases. Following success in this phase, the vaccine is released to the general public. Phase 4 consists of monitoring the implementation of the vaccine on a large scale and identifying side effects that need to be addressed. Each phase requires an increasing number of volunteers, starting with only a few tens of volunteers in Phase 1 and increasing to thousands (or even millions) by Phase 4 (Fiocruz, 2020).
How did they develop a vaccine so quickly? Doesn’t it normally take years?
There are multiple reasons for the speed with which a COVID-19 vaccine was developed.
Pre-existing knowledge: Research teams were able to build understanding based on an earlier coronavirus: Middle East Respiratory Syndrome (MERS). This allowed them to discern how COVID-19 enters cells within two weeks of its discovery (NIH).
New technology: When SARS-CoV-2 was discovered, the newly available mRNA technology was readily available for vaccine development. COVID-19 provided an opportunity for countries to invest in this technology to aid advancement (Harrison, 2020).
Financial resources: COVID-19 required a global response that attracted numerous investments into the research and development of a vaccine.
So, the vaccine is ready for widespread use – what next?
Once the vaccines are suitable for mass inoculation, they are bottled, labelled, and stored. Prior to distribution, the vaccine needs to be authorized by the local sanitary regulation agency, or similar, in each country. In some countries, this authorization is dismissed if conditions imposed as part of local laws are met. Brazil, for example, instituted a “COVID Law” (“Lei da COVID”, in Portuguese) that gives Anvisa (the Brazilian Sanitary Agency) 72 hours to approve a vaccine where it has been approved by the regulatory agencies in Europe (European Medicines Agency, EMA), the United States (Food and Drug Administration, FDA), Japan (Pharmaceuticals and Medical Devices Agency, PMDA), or China (National Medical Products Administration, NMPA). After this period lapses, authorisation must be given by the State independent of the national regulatory agency (Brazilian Covid Law, 2020).
What makes vaccine distribution so complicated?
While there are several angles to consider, we consider a few here. Legal, with consideration for the World Trade Organization (WTO). COVAX and the potential for building solidarity. Humanitarian, focused on bringing innovation and expertise to low and middle-income countries (LMICs).
For high and low-income countries there are tremendous technical challenges to producing the worlds first mRNA vaccine, which is COVID-19, and also logistical complexities which are highlighted in this report on Critical Vaccine Delivery: A Challenge for the Global South.
The WTO’s new Director-General, Dr Ngozi Okonjo-Iweala, has asked WTO Members to ‘intensify cooperation on promising new vaccines, therapeutics, and diagnostics’ – a step in the right direction. The COVAX facility holds potential for building solidarity and delivering vaccines quickly and affordably to poorer countries. However, many countries cannot afford these expensive vaccines and lack the technology to develop them (WTO, 2021).
‘Equitable distribution, now – is in our hands,’ said Director-General of the WHO Tedros Adhanom Ghebreyesus, on 17 March, upon describing the request for voluntary licensing, encouraged by the WHO’s own Covid-19 Technology Access Pool initiative, and also through providing provisional intellectual property waivers.
Promoting technology transfer between high-income countries and LMICs is also important even beyond COVID-19 for wider technological availability and capacity. One example of such bidirectional collaboration is The Uganda Virus Research Institute working with both Imperial College London and the NHS to develop a self-sustaining blueprint to bring RNA manufacturing platforms and vaccine technology to LMICs to create a rapid response platform for emerging infections (Imperial, 2021). These, however, are few – and more are needed.
19 March 2021
By Ana Clara De Queiroz
Public Health Pathways trend reporter, biologist and teacher in Brasilia.
