Rami Bechara

At least 35 groups, 7 pharmaceutical and biotech companies, Pasteur Institute and 7 different Universities including Oxford, Imperial, and Pittsburgh are working on COVID-19 vaccines, at a pandemic speed … 3 trials begun.

Across the world, countries continue to combat the deadly coronavirus. We witnessed different approaches including social distancing, massive testing, quarantine and isolation, and even contact tracing. However, according to a study by Ferguson et al, it is likely that transmission will quickly rebound if interventions are relaxed in the near future (Fig.1). Thus, there is a major unmet need for an effective strategy to eradicate SARS-CoV-2, the virus that causes the coronavirus disease 2019 (COVID-19). Therefore, the development of COVID-19 vaccines is a priority for ending this pandemic. Indeed, over the past century, some of the most important medical breakthroughs were linked to the development of vaccines to protect humans against viruses such as polio and smallpox. More recently, an H1N1 influenza vaccine was developed relatively rapidly to respond urgently to epidemics of H1N1 influenza. Here, I will describe the state of art of COVID-19 vaccines with some encouraging news in trying times.


Fig.1 Principles of vaccination & social distancing applied theoretically for COVID-19

Vaccination - a quick refresher
Vaccination is an approach designed to artificially help the body to defend itself by generating, usually, an expanded army of pathogen-specific memory lymphocytes. In principle, a vaccine against infection is a modified form of a natural pathogen, which may be either the whole pathogen or one of its components. Following exposure of the immune system to an antigen, pathogen-specific lymphocytes are “primed” and often continue to circulate in the blood (and also reside in the bone marrow) for many years. When the natural pathogen attacks, these memory cells respond very rapidly by producing antibodies to reestablish protection. This is what we call “active immunity”.

  • Antigen
    • Substance capable of inducing an immune response

    • Protein produced by B lymphocytes to help eliminate an antigen

    Active Immunity
    • Protection produced by the person’s own immune system
    • Often lifetime

COVID-19 Vaccine Tracker: Over than 40 candidates
Different worldwide organizations, pharmaceutical companies and universities have called for targeted efforts to develop therapies against COVID-19. Consequently, at least 40 COVID19 candidates were described so far and, by the time I was writing this article, three of them have entered “Phase I” of clinical trials, the first of three stages of human testing before drug approval. More precisely, during Phase I testing, researchers test the safety of the candidate vaccine but we won't know if it's effective – if humans will develop enough virus-neutralizing antibodies – until Phase II is studied. This is clearly the result of scientists with different expertise working together and being able to respond quickly.

We should keep in mind that vaccine development, similarly to other medications, is a very lengthy and expensive process. However, during this pandemic many steps of vaccine design are executed in parallel before confirming a successful outcome of another step, hence resulting in shortening manufacturing-time while at the same time increasing financial risk. For instance, mRNA-1273 candidate vaccine was rushed to human trials before it was even tested in animals based on previous data related to other coronaviruses, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Additionally, the company is hopeful that their vaccine may be available by fall 2020 mainly for vulnerable groups.

Ad5-nCov is another promising candidate by CanSino, China. Phase I testing is underway in China. It is worthy to mention that CanSino has already produced a nearly identical vaccine to protect against Ebola. ChAdOx1 is also a top front-runner vaccine for COVID19. Interestingly, the vaccine will be simultaneously tested for both safety (Phase I) and efficacy (Phase II).

    • Candidate: mRNA-1273
      Company: Moderna biotech-USA
      Ingredient :Genetic materials (mRNA) that codes for the spike protein of the virus
    • Candidate: Ad5-nCoV
      Company: CanSino - BiologicsChina
      Ingredient: Recombinant engineered coronavirus
    • Candidate: ChAdOx1
      Company: Oxford Vaccine Group – University of Oxford
      Ingredient: Inactivated (non-infectious) virus

Old but gold

Different epidemiological studies have pointed to a correlation between the rates of COVID-19 morbidity and anti-tuberculosis vaccination (BCG). Researchers in different countries, including Pasteur Institute-France, are investigating whether BCG could reduce the intensity of SARS-CoV-2 infection. Indeed, previous studies showed a non-specific protective effect of BCG against infections, particularly respiratory infections.

PittCoVacc is a “highly-scalable” potential vaccine developed by the University of Pittsburgh. It is essentially made using lab-made pieces of viral protein integrated into the original scratch method used to deliver the smallpox vaccine to the skin. When tested in mice, PittCoVacc generated enough antibodies against SARS-CoV-2. However, we still don’t know the potential duration of the acquired immunity.



Despite all the efforts described above, Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases (NIAID), predicts a vaccine “is going to take a year, a year and a half, at least.” Indeed, there are many challenges to take into consideration during vaccine development. Determining the dose to administer, the side effects and manufacturing problems can all cause delays. Additionally, the potential duration of immunity against COVID19 is relatively unknown. Thus, whether a single-dose vaccine will confer immunity is still elusive.

Taking into consideration all the above mentioned points, I can’t tell you exactly when the vaccine is coming…Nevertheless, the beginning of trials is just one bright light in some devastating news across the world.

Ferguson NM, Laydon D, Nedjati-Gilani G et al. Imperial College COVID-19 Response Team Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand. https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-NPI-modelling-16-03-2020.pdf