One of the biggest questions people are asking is when we are going to get a vaccine. Presumably, designing an effective vaccine and wide scale vaccination campaigns will ultimately eradicate the virus or at least allow those vaccinated to return to a new normal. Research is flowing into COVID-19 research of all types, with Congress approving a $3.6 billion just for research (1). Of that, $1.53 billion goes to the National Institute of Allergy and Infectious Disease, a National Institute of Health subsidiary focused on infectious diseases. Outside of the U.S., other countries are also working towards a vaccine, especially China. There could very well be multiple approved vaccines depending on how it plays out.
A vaccine is a way of teaching the human body to fight a pathogen, giving it a tag so the next time it sees the pathogen, it knows what to do (2). The human body constantly is presented with microbes and other organisms. Passive and active immunity is required to discriminate between the self and the outside and to eliminate pathogens. Active immunity remembers pathogens for a lifetime whereas passive immunity only lasts a few weeks or months at most. After surviving a severe infection, special cells called memory B cells will remember the pathogen and provide long-lasting immunity (2). Vaccines are a way of getting that long-lasting immunity without going through the infection.
Different methods are used to produce immunity. One is live-attenuated vaccines, which rely on cloning a weakened strain of the virus to infect the subject and gain immunity without suffering a severe infection (3). People do not tend to get sick even though they are getting infected and the virus is multiplying in them. These vaccines include the MMR vaccine, chickenpox, yellow fever, smallpox, and rotaviruses (4). Codagenix and the Serum Institute of India are working together to weaken SARS-CoV-2 by making changes to its genetic code (5). Not many other institutions are doing this. These vaccines require many human trials and are very risky but have all of the components of a virus so should work in the long run. This is not the fastest way of making a safe and reliable vaccine. Other methods are required.
Another type of vaccine is inactivated vaccines, which rely on taking the live virus and weakening it with chemical treatment (3). This is hard to get right but takes advantage of chemistry as a discipline in itself more than others. The seasonal Influenza vaccine, Hepatitis A, Polio, and Rabies are all inactivated doses of the virus (4). Sinovac is working on this and is currently in phase 3 trials, with large scale human trials. Sinopharm along with the Wuhan Institute of Biological Products and the Beijing Institute of Biological Products also are using inactivated vaccines (5). This is a common approach among disciplines. The Chinese military has units which are approved of taking these vaccines, showing their confidence in this relatively straightforward method.
The third type is viral vector vaccines, relying on making recombinant viruses like a flu virus with a gene expressing SARS-CoV-2 surface proteins to induce an immune response (4). This is definitely possible and could very well be safer than using a live form of the virus. The question is how effective these surface proteins alone will be in inducing a strong immune response. The University of Oxford is partnering with Astrazeneca to make this type of vaccine, with phase 3 trials starting and already with the data from previous trials (5). The UK opted out of the Inclusive Vaccines Alliance, an alliance with currently four European members whose goal is to manufacture successful vaccines in Europe. They are hedging their bets mostly on the Astrazeneca vaccine given how well-developed and its stage. A new trial has begun this month with 30,000 people in it (6). 25 groups, including the phase III Beijing Institute of Biotechnology, are working on this model (3, 5).
The U.S. is most concerned with the Moderna vaccine. Moderna is well-funded by the NAIAD to produce an RNA vaccine, relying only on RNA fragments to enter cells through LNPs or lipid membrane vehicles (5). No successful vaccine has so far been approved for human trial using an RNA vaccine (3). But that hasn’t stopped Moderna. It recently announced (July 27) that it has begun its first of many phase III trials consisting of 30,000 people each, putting it not too far behind in the international race (7). Pfizer is another big name working on an RNA vaccine as well, but still in phase II.
The fourth type is DNA vaccines, which inject DNA fragments to do roughly the same thing as the RNA vaccine but require electroporation or another injection method to enter cells. The leading candidates for this type are Inovio Pharmaceuticals in phase II, Osaka University in phase II, Genexine Consortium, and Cadila Healthcare, all in Phase 1 or 2 trials. Inovio for example has a device that will build a slow voltage to move the DNA fragments into cells for the body to recognize and start building its own vaccines to it. Neither DNA nor RNA vaccines have been approved for human use yet.
Finally, the fifth type uses protein subunits, either native or recombinant, to inject into the body without a viral casing (3). These may require “adjuvants” or immune stimulating substances along with the vaccine and multiple doses to be most effective. Anhui Zhifei Longcom Institute of Microbiology and the Chinese Academy of Sciences are working on protein subunit synthesis and testing, having already done previous work with it on the Middle East Respiratory Virus (MERS) and repurposing it towards SARS-CoV-2 (8).
So many solutions are possible, yet so many are divided. Many of these vaccines will never end up injected into any person. Only a handful will get approved. It is incredible and yes unprecedented to make a vaccine in less than two years starting from almost scratch. The research and clinical trials have all been accelerated. But a timeline of 12 to 18 months is still extremely optimistic (9). It is just not possible to get through all of the research, modifications, safety, approval, manufacturing, and distribution networking in such short notice. The country you live in will determine the vaccine you receive. Despite the political ramifications of vaccine research, distribution, and profit, scientists and institutions continue to honor partnerships and work together to heal the world.
Edited by: Keshav Kailash
Illustrated by: Lucy Chen