I have read in a recent issue of New Scientist, of March 20, under the above title by Carrie Arnold, a science writer based in Virginia, USA, about the coverage for the search of a vaccine against the present SARS-CoV-2, aka Covid-19. A summary of the article presented here is aimed at enlightening the reader in simple terms about the whole process of developing a vaccine as fast as possible amid the present pandemic.

Normal steps in vaccine development

1. Search for a prototype. This can take years. However, thanks to new technologies, such as the use of computational models, after the announcement by the Chinese officials of the important genetic sequence for the new virus, 2019-n-CoV or SARS-CoV-2, published internationally, a molecular geneticist from a pharmaceutical firm in the United States produced within 3 hours a prototype of the vaccine for initial testing. The virus comprises the genetic material, RNA (Ribonucleic acid) enveloped in a protein coat. The outer protein spikes give the appearance of a crown (corona). Several studies are in progress to understand how pathogens interact with the body and immune system before developing a vaccine. Only one in four candidates makes it to the clinical trial stage.

2. Animal trials. This is to demonstrate safety and test immune responses respectively generated by the vaccine. It is important to test in animals resembling man and it is not appropriate to use dogs because their physiology is different. Hence the invaluable role of monkeys. This safety step can be a trade-off when time is of the essence.

3. Phase I Human Trials. 20-28 individuals are selected to demonstrate safety and ensure that any side effects are not too severe.

4. Phase II Human Trials. Larger groups are chosen to test again for efficacy. This step can also be skipped when there is an urgent need. At this stage, an application can be made for regulatory approval.

5. Phase III. Hundreds and thousands of people are tested to clearly evaluate both efficacy and safety.

6. Regulatory Approval. After examining clinical trial evidence, the regulatory bodies determine whether the vaccine can be used for public use and also imposing the collection of follow-up data. In the United States, the Food and Drug Administration (FDA) is the regulatory body whilst in Europe, it is the European Medicines Agency. The World Health Organisation (WHO) also issues guidance documents to national regulatory authorities and manufacturers.

7. Mass Production. This can then be carried out under strict quality control and consistency standards.

8. Public Access. Government and Public Health Authorities will have to determine which group of people will get the vaccine first.

Mode of action

All vaccines work by ‘tricking’ the body into believing it has been exposed to a pathogen (e.g. a virus that can cause disease). This causes the immune system to respond with antibodies and specialised cells (T-Cells) to neutralise and kill the invader. Afterwards, some of these remain in the circulation, ready for action in case one is exposed to the actual infection. The more closely a vaccine mimics the disease the more protection it provides.

Sources of vaccines against viruses

(a) Live-attenuated vaccines use actual viruses that have been altered to prompt an immune response.

(b) Inactivated vaccines are obtained by growing huge amounts of virus in vats and are killed by heat or chemicals.

(c) Subunits vaccines contain just pieces of a pathogen that activate the system. It can be polysaccharides (sugars), proteins or a mixture of both.

New strategies

Scientists in Hong Kong took advantage of the genetic sequence published by the Chinese and showed similarities between the new virus and past coronaviruses. 90% of its DNA was similar to SARS-CoV (2003).

An immune response was also most strongly felt from the protein spikes that form the now familiar crown (corona) surrounding the genetic material. One of five sites were found to be similar between the new and earlier SARS viruses and hence an important target for any new vaccine. Already 35 candidate vaccines have been produced, 6 of which were backed by the Coalition for Epidemic Preparedness Innovation (CEPI), created in 2017 and funded by Bill and Melinda Gates; the Wellcome Trust, and several governments for better and faster rapid response.  

Money is critical to vaccine development. It is reported that 350 million dollars would be required very soon to meet the accelerated timeline of creating a vaccine for Covid-19 within 12-18 months. Without CEPI, this venture is unattainable. Universities, Research Centres and pharmaceutical firms worldwide, with the support of CEPI, are collaborating in the quest to obtain a suitable vaccine against Covid-19. Covid-19 can cause severe pneumonia and is a deadly virus.

DNA/RNA molecules are also being tried in the search for a vaccine, although as such they do not create an immune response. The DNA–RNA–Protein dogma is well-known and could be exploited in, thus producing suitable proteins on muscle or skin cells which in turn could as well trick the immune system into thinking the body has been invaded by a pathogen which leads to the creation of special cells (T cells) and antibodies.

No such vaccines have been approved. Direct injection in blood is not feasible as blood enzymes will chop the DNA or RNA molecules. Other approaches, such as enveloping the vaccine genetic material in a protective core, are being exploited. There are concerns about DNA-based vaccines. They could affect one’s own genes and spur harmful immune reactions.

Caution and optimism

Striking a balance between speed and safety is always going to be a challenge. If a vaccine takes too long to develop, the initial outbreak may be over and robust data in terms of enough evidence about safety and efficacy required for regulatory approval cannot be achieved. This was a problem with the Ebola outbreak in West Africa in 2004. But later, the Ebola vaccine known as Ervebo satisfied these requirements for approval after a larger outbreak and bigger trials. Also, no SARS vaccine made it beyond Phase I safety trials.

Assuming everything going well and faster-than-ever- progress through each step in the process, the researchers think there is no doubt a successful vaccine against Covid-19 will be found. It is early to say which candidate will be ready first. Greg Poland, from Mayo Clinic in Minnesota, USA, concluded: “We’re building the plane as we’re flying.” In the meantime, we have the first human trials by the group at Oxford University. The team leader, when interviewed, sounded very optimistic.