The Race to a COVID-19 Vaccine
Updated: Jul 30, 2020
As COVID-19 cases continue to rise with more than 14 million confirmed world-wide, the race to a vaccine becomes increasingly more important. There are currently 25 candidate vaccines in clinical trials and 145 candidate vaccines in pre-clinical trials, with many progressing swiftly through clinical phases. The current speed of vaccine development is not only impressive, but unprecedented; vaccine development is normally measured in decades, but with current manufacturing platforms, structure-based antigen design, protein engineering, and gene synthesis, a vaccine may become available as early as the end of 2020.
In order to fully tackle COVID-19 on a global scale, a combination of vaccine approaches is necessary. There are currently various types of vaccines being developed including live-attenuated virus vaccines, inactivated whole-virus vaccines, recombinant protein vaccines, nucleic acid vaccines, and viral-vector vaccines. Each vaccine approach has strengths and weaknesses, with some of the assessment areas being immunogenicity (the ability of an antigen to provoke an immune response), safety, speed of development, and tolerability. While many candidate vaccines are making progress, there are a few that stand out in terms of what they have already achieved.
One candidate vaccine that has entered phase 3 clinical trials is the recombinant vaccine AZD1222 (ChAdOx1 nCov-19) created by the University of Oxford and pharmaceutical company AstraZeneca. The vaccine includes a replication-deficient adenovirus that will carry the DNA of the spike protein of SARS-CoV-2 that allows the virus to infect human cells. This is a viral vector vaccine that in this case uses a chimpanzee adenovirus as a vector to carry the spike protein DNA into human cells; this confers immunity to the spike protein and therefore doesn’t allow the live virus to enter human cells in the future. The study compared subjects given the chimpanzee adenovirus-vector vaccine to subjects given a meningococcal conjugate vaccine as a control. Some mild reactions were seen in the experimental group including pain, chills, and headaches but there were no serious adverse events. The AZD1222 vaccine resulted in higher antibody levels, neutralizing antibody responses and increased T-cell responses compared to the control group. Neutralizing antibodies are important because they defend cells from pathogens by binding to them and neutralizing their effects biologically. T-cells play a central role in the adaptive immune system by killing infected host cells and activating other immune cells. The combination of both neutralizing antibodies and an effective cell mediated response (T-cells) is critical when developing a COVID-19 vaccine. The AZD1222 has thus far been proven relatively safe and effective, and is quickly moving towards the finish line of approval.
Another candidate vaccine that has made significant progress is the adenovirus type-5 vectored COVID-19 vaccine developed by the CanSino vaccine company in Wuhan, China. Similar to Oxford’s AZD1222 vaccine, this is also a viral vector vaccine that uses a type-5 adenovirus as a vector to insert the spike glycoproteins of SARS-Cov2 into human cells. In the phase 2 clinical trial, 2 different amounts of the vaccine were administered to healthy adults and closely assessed for 28 days. Again, an increase in antibodies and T-cell responses was seen in most participants, with many mild and a few severe adverse reactions (none were serious). The lower dose was shown not only to produce fewer adverse reactions, but also to produce a higher antibody response, a result which was unexpected. This vaccine is also considered both safe and effective.
One more candidate vaccine is using a different method: the mRNA-1273 vaccine created by Moderna in Cambridge, MA uses cutting edge mRNA technology that has yet to be used in vaccine production. Unlike most vaccines which involve using inactivated disease-causing organisms, mRNA vaccines use only the mRNA strand that codes for the disease-specific antigen (toxin that will produce an immune response), and thus aren’t created using infectious elements. While mRNA vaccines are cheaper and faster to produce, certain consequences such as unintended immune responses could occur. Despite the potential roadblocks with using mRNA as the vaccine component, the phase 1 trial of Moderna’s vaccine produced an immune response similar to that seen in people previously infected with COVID-19 and the company says it is on track to be able to produce 500 million to 1 billions doses by the start of 2021. A few more notable vaccines in promising clinical development are Novavax’s protein subunit vaccine, Pfizer’s BNT162b2 mRNA vaccine, and Imperial College’s mRNA vaccine.
While this progress is promising, the availability of a vaccine isn’t enough to guarantee broad immunological protection; the vaccine must be accepted by both the health community and the general public even before it is distributed. As soon as clinical trials have been completed and vaccine efficacy has been verified, the vaccine should be rapidly and justly distributed to the public; potential obstacles such as vaccine hesitancy stand in the way. Vaccine hesitancy would be a major barrier for the achievement of herd immunity, or most of the population becoming immune to an infectious disease. Since some people will not be able to be vaccinated due to factors such as old age and being immunocompromised, a vaccine refusal rate higher than 10% could be a major set back from the goal of defeating the virus. There are certain actions that can be taken to prevent people’s vaccine hesitancy and refusal, including correcting certain misinformation presented in social media regarding vaccines, and encouraging frontline health workers to promote the benefits of vaccination. In addition to those who work in medicine and public health, cultural leaders of certain communities should also be used to promote vaccination and spread culturally relevant messaging, as they are likely very trusted in their communities. In order to swiftly begin vaccinating as many people as possible, especially those at highest risk for complications and those in heavily affected communities, a robust education regarding the necessity of vaccines needs to be used.
The current work being done on COVID-19 vaccines is a promising step in the right direction, but without equal vaccine distribution amongst communities and a thorough understanding of the benefits, it will not be enough to control this pandemic.