A Vaccine For The Coronavirus – The Global Efforts To End The Pandemic

With the coronavirus still wreaking havoc around the world and its collateral damage destroying various countries’ economy, a vaccine is needed now more than ever. At the time of writing this, 7 months have passed with no clear news on a potential vaccination and an end to the spread of COVID-19. So, what are scientists trying to do, has progress been made, and is there still hope for an expeditious end to the worldwide pandemic?

What is a vaccine and what types are there?

A vaccine is something that is used to stimulate an immune response in the body and produce immunity against a specific pathogen. In short, the body’s immune cells are exposed to proteins and other substances that belong to pathogens that act as antigens to the cells. Eventually, B cells are stimulated to differentiate into plasma cells. Plasma cells produce different classes of immunoglobulins, more commonly known as antibodies, that are complementary in structure to bind to and deal with a pathogen’s antigens. Because of this, they are the key immune cells for immunological memory and immunity as they produce memory cells that remain in the blood and can produce the most specific antibodies at a quicker rate – immunological memory is defined as the ability to rapidly produce large concentrations of high-affinity antibodies after a second infection and presentation of the same antigen.

Antibodies binding to antigens

Vaccines can manipulate the body’s immune response to do this and achieve immunological memory and immunity using different vaccine candidates. Vaccines can elicit an immune response in many different forms. One is attenuation, which involves the virus being passaged through various cells inducing mutations in its genome which reduces virulence. Another is inactivation which uses chemicals or UV radiation to reduce the pathogen’s infectivity without reducing its antigenicity – the pathogen’s ability to induce an immune response. There’s also a fractionation technique which involves centrifugation of the pathogen’s components. This is followed by isolation of the specific molecule that acts as an antigen for use in vaccines. As well as this, there is a cloning method. This is when specific genes are pulled from the pathogen and expressed in bacteria using recombinant technology. The bacteria then express the desired antigen which is isolated and used in vaccines.

Why are vaccines so difficult to produce?

There are many different ways a vaccine can be created and to do so, the best method is needed; one that is cheap, safe, effective, easily transported, can be stored at cooler temperatures, long-lasting, and a good route of administration. There are also many barriers to producing an effective vaccine as well as problems with getting the vaccine administered worldwide. The success rate of vaccine development alone is only 6%. Other problems include both long- and short-term side effects that have to be studied for extended periods of time before global use, the cost of research, the ethics, and those who abstain from the vaccination programme and refuse to be vaccinated. As a result, a vaccine can be delayed for months or years, and even when it is finally created, herd immunity is at risk if lots of people do not get vaccinated.

So, what is the current status of a potential vaccine for SARS-CoV-2?

Leading the efforts of ending this pandemic and finding an efficient vaccine for coronavirus is the University of Oxford. They are currently developing a recombinant vaccine using AZD1222 as a candidate which is currently going into phase III trials. They have announced an agreement with the biopharmaceutical company AstraZeneca for a large-scale manufacturing and possible distribution of the potential vaccine. AZD1222 utilises an attenuated chimpanzee adenovirus that carries the DNA for the SARS-CoV-2 spike (S) glycoprotein which acts as an antigen. It has been genetically modified so that it cannot replicate in human cells but the recombinant form is immunogenic which allows potential B cell formation and long-term immunity to coronavirus. Since the S glycoprotein is required to bind to the ACE2 receptor of the host cell to allow cell entry into the cell, the antibodies that are raised against the S glycoprotein will prevent the coronavirus from binding to the ACE2 receptors on respiratory tract cells that act as a doorway for the virus to replicate within it. Phase III of the AZD1222 vaccine trial includes treating healthy adults aged 18-65 who work in both front-line health services and the general public involving 10,000 participants. It will also include some older adults and young children to investigate efficacy in these categories. Optimistically, as of June 13th, AstraZeneca made an agreement with Europe’s Inclusive Vaccines Alliance to supply up to 400 million doses of the newly developed vaccine candidate starting at the end of 2020.

Moderna, an mRNA therapeutics company, is also working on a vaccine for the novel coronavirus using a different method. They make vaccine candidates based on mRNA. mRNA is similar to DNA, however, it has the ability to leave the cell’s nucleus and travel to the ribosomes where it directly codes for amino acid chains that produce proteins. Their vaccine candidate is mRNA-1273. This was produced after the SARS-CoV-2 genome was sequenced and the DNA sequence for the S glycoprotein was established. The corresponding mRNA sequence was then produced. This mRNA was optimised for high-level and durable protein production and encapsulated by lipids. By doing this, when injected, the lipid-encapsulated mRNA is taken up by the cell and the mRNA is released allowing translation into the encoded protein – in this case, the S glycoprotein. This acts as an antigen that is subsequently degraded by the proteasome into small fragments that are transported to the endoplasmic reticulum and processed on MHC class I complexes. These are expressed on the cell surface and allow CD8+ T cells to recognise them and trigger an immune response which eventually leads to B cell production, proliferation, plasma cell production, antibody secretion, and memory cell formation. As of May 29th, Moderna’s mRNA-1273 vaccine candidate has entered phase II clinical trials and the first cohort of two healthy 300-participant groups aged between 18-55 has been dosed with the mRNA-1273 vaccine. They plan on giving a second dose 28 days later. This aims to assess the safety, reactogenicity, and immunogenicity of the vaccine. Moderna has also started to prepare for a quick acceleration of the manufacturing capabilities to allow for the possible manufacturing of millions of vaccinations if these clinical trials prove to be safe and efficient.

Another potential candidate for a vaccination includes BBIBP-CorV, an inactivated SARS-CoV-2 vaccine candidate developed by the Beijing Institute of Biological Products partnered with China National Pharmaceutical Group. They used b-propiolactone to inactivate the virus meaning it can no longer infect cells. However, since the virus still contains viral proteins that act as antigens, it is still recognised by the immune system and stimulates an immune response with potentially long-term protective immunity. BBIBP-CorV is currently in phase I/II clinical trials involving 1,000 participants after successful preclinical trials that showed a strong production of neutralising antibodies in 6 mammalian species – rhesus macaques, cynomolgus monkeys, guinea pigs, mice, rats, and rabbits. The results from these studies also showed no signs of complications and safety concerns.

Is there hope for a vaccine in 2020?

Around 100 vaccines are under development around the world and the race to find the most efficient, safe and best vaccine candidate is well underway. It is evident that a successful vaccination is needed now more than ever as surges of new infections are still making their way through different countries; America alone has seen recent spikes in the number of cases with 21 states reporting an increase due to the current Black Lives Matter protests that are currently dominating the streets. As time goes on, scientists will continue to make more breakthroughs but also discover flaws in current research programmes that will grind the potential production of a vaccine to a halt. Until a successful vaccine candidate is found and manufactured for global use, all we can do is ‘stay alert, control the virus, save lives’.