Coronavirus Vaccine Development – Look Before You Leap

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Nothing short of a medical miracle, coronavirus vaccines may be on the verge of being available to the public. Just months after its rapid spread throughout the world, scientists are making great strides toward delivering much-needed protection against the deadly virus. However, as much as a vaccine offers hope, a blind rush into delivering one would be a blatant act of negligence. Now, perhaps more than ever, we must strive to maintain our filters of scientific skepticism.

Coronavirus (SARS-CoV-2) Biology

At the time of writing, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, referred to simply as coronavirus) infection is responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). COVID-19 causes flu-like symptoms in the majority of the population but is characterized by shortness of breath and respiratory dysfunction in some individuals, with cardiovascular complications and multiorgan failure also reported1.

coronavirus daily cases as of may 22
SARS-CoV-2 confirmed cases worldwide continue to rise (Source)

The coronavirus is also incredibly infectious, evidenced by the mere months separating the first recorded outbreak in Wuhan from its escalation to pandemic status. Along with human to human transmission, the virus has been shown to be active on surfaces for up to several days2. Multidisciplinary research teams have worked toward a better understanding of this dangerous microbe, with the aim of developing a reliable defense against it.



Coronavirus Vaccine Candidates

When a new pathogen enters the body, our immune system takes some time to identify it. Once it does so, our immune cells can create pathogen-specific proteins called antibodies that help to facilitate their destruction. We then retain these proteins, which can quickly identify the virus in case of future infection and trigger a rapid immune response.

All vaccines aim to help our body attain immunity – a state where it is ready to develop a rapid immune response – without prior exposure to the pathogen. That would defeat the purpose of vaccination, wouldn’t it? In order to develop a vaccine against the coronavirus, researchers are studying the effectiveness of different methods that can bestow immunity.

Inactivated Viruses

The simplest approach to developing a vaccine is to introduce the entire virus into an individual, without extensive engineering to its structure. Viruses are first weakened or inactivated so that they do not end up causing an infection, with several methods available to achieve this. At least one drug candidate in this group has been cleared to move on to phase 2 clinical trials.

Viruses can be genetically modified, treated with chemicals or heated to remove or reduce their ability to function; the challenge is ensuring they retain the ability to induce the appropriate immune response. Inactivated viruses might not produce as strong an immune response as the real thing, so efficacy might be an issue. On the other hand, any vaccine created with this method requires extensive safety testing because of the increased possibility of causing a real infection.

Virus Genetic Material

The genetic material for coronavirus is stored in its entirety on a single strand of RNA, which in turn codes for its proteins. It uses these proteins to hijack our cells and forces them to produce more copies of RNA, creating even more viruses. Knowing the viral genome, we can isolate a certain segment of its genes that code for a particular protein. These segments can be engineered and delivered into our own cells, prompting them to produce that protein.

Several groups are utilizing this method for creating a coronavirus vaccine, with at least one candidate having success in phase 1 clinical trials.

Viral Protein Fragments

To go a step further, proteins fragments that mimic those found on the virus can be introduced directly into our bodies. These proteins are usually found on the virus surface and are unique to the virus, hence exposure to them should stimulate an immune response.

Viral protein fragments are a therapeutic challenge, due to the difficulty of designing and delivering such a drug; consequently, there is little research interest in this method developing a coronavirus vaccine. That being said, a New Zealand based group is attempting to design ‘beads’ coated in synthetic proteins similar to the surface spike proteins found on the coronavirus outer coat.



Precautions in Vaccine Development

However, researchers must tread carefully throughout the development of a suitable vaccine, as many factors remain unclear. U.S. pharmaceutical company Moderna faced backlash after announcing success in its vaccine candidate without presenting sufficient data, let alone in a peer-reviewed journal. Early successes may not translate into a safe and effective drug, although news outlets can sometimes be partial to bouts of exaggerated reporting. In spite of the enormous pressure and desperation surrounding the need for a coronavirus vaccine, there can be no compromise for the basic principles of the scientific method.

Robust Clinical Trials

Clinical trials begin with animals (rodents, primates) before moving on to humans, although several trials are performing this concurrently to save time and money. Despite the enormous costs associated with clinical trials and drug development, it is a necessary process that every drug candidate must be put through. Putting timelines on a readily available vaccine is unrealistic, especially with drug candidates currently still in the early stages of clinical trials.

In the face of economic and social pressure, clinical trials must be robust and well-designed, with a large enough sample size and practice that minimize bias. Regulatory processes such as clinical trials prevent the risk of adverse effects in the public, therefore decisions based on them cannot be hasty. It remains important to assess the safety and efficacy of a drug in a systematic manner using reliable, science-based data.

Effectiveness of a Vaccine

Solid data must be provided to give evidence for a potential vaccine’s safety and efficacy. Several trials have not presented data on the levels of coronavirus antibodies after administration of the vaccine. It is still unclear how much antibody production is required to confer immunity to future infections. Patients who have recovered from a coronavirus infection seem to have low levels of required antibody, thought to be too low to even prevent reinfection3. Furthermore, coronavirus antibody test kits are still in the developmental stage, with issues on specificity due to the similarity between Sars-CoV-2 and other coronaviruses.

Because vaccines are supposed to provide protection against future infections, extensive data must also be collected on its effectiveness in the long term, even after its introduction to the market. Prior studies show that levels of antibodies against other coronavirus strains drop rapidly after recovery, while for other strains even high levels of antibodies in an individual may not completely prevent future infections4,5.

Vaccine Safety

An additional issue that arises with new coronavirus vaccines is the possibility of antibody-dependent enhancement (ADE). In cases pf ADE, previously vaccinated individuals develop a more severe form of infection when exposed to the virus. One such vaccine developed for SARS-CoV in 2004 showed severe ADE during animal studies, causing research to be halted6.

The World Health Organization reports that around 90 vaccine candidates are currently being researched or trialed. There is genuine optimism that a vaccine will be developed through collaborative efforts, as demonstrated in recent medical triumphs against the ebolavirus.

The United States government has made bold claims that a Sars-CoV-2 vaccine will be available to the public by the end of 2020. But safety and efficacy cannot be compromised; timelines and predictions could (and should) be thrown out the window at a moment’s notice. Once a coronavirus vaccine becomes available, millions of vulnerable individuals will rush to get themselves immunized. It is important that we take the necessary steps to ensure their safety; for while vaccines provide hope for a COVID-19 free world, they are also a reminder for caution.



Reference

  1. Cascella, M., Rajnik, M., Cuomo, A., Dulebohn, S. C., & Di Napoli, R. (2020). Features, evaluation and treatment coronavirus (COVID-19). In Statpearls [internet]. StatPearls Publishing.
  2. van Doremalen, N., Bushmaker, T., Morris, D. H., Holbrook, M. G., Gamble, A., Williamson, B. N., … & Lloyd-Smith, J. O. (2020). Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. New England Journal of Medicine, 382(16), 1564-1567.
  3. Robbiani, D. F., Gaebler, C., Muecksch, F., Lorenzi, J. C., Wang, Z., Cho, A., … & Oliveira, T. (2020). Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals. bioRxiv.
  4. Tang, F., Quan, Y., Xin, Z. T., Wrammert, J., Ma, M. J., Lv, H., … & Cao, W. C. (2011). Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study. The Journal of Immunology, 186(12), 7264-7268.
  5. Holmes, K. V. (2003). SARS coronavirus: a new challenge for prevention and therapy. The Journal of Clinical Investigation, 111(11), 1605-1609.
  6. Weingartl, H., Czub, M., Czub, S., Neufeld, J., Marszal, P., Gren, J., … & Grudeski, E. (2004). Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. Journal of Virology, 78(22), 12672-12676.

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