Preliminary findings show a COVID-19 vaccine from Oxford/AstraZeneca is well-tolerated and induces an immune response.
Over the past few months, it has seemed that we are being flooded with bad news. Thankfully, promising data from a phase I/II clinical trial was released yesterday regarding a potential vaccine against SARS-CoV-2 developed by Oxford University and AstraZeneca. Although there is still a lot of work to be done, I am cautiously optimistic about where this vaccine is headed!
The Vaccine
Traditional vaccines use inactivated forms of a virus to induce an immune response. The Oxford/AstraZeneca vaccine, called ChAdOx1 nCoV-19, is different and more like a trojan horse. It uses a chimpanzee adenovirus that can not replicate and is harmless to humans as a vector or “trojan horse” to gain entry into a human cell. The “trojan horse” contains the genetic material for the SARS-CoV-2 spike protein, which is expressed on the surface of the virus and is critical for viral entry into human cells (see Figure). Following vaccination, cells will produce the spike protein, hopefully activating an immune response against the spike protein. The goal is to induce immune “memory”, meaning some immune cells will persist for a long time. If a vaccinated individual is later infected, these immune cells will remember the spike protein on SARS-CoV-2 and activate a quick and effective immune response.
Clinical trial info
1077 healthy participants aged 18-55 were randomly assigned to two groups. One group received the ChAdOx1 nCoV-19 vaccine, and the other group received a meningitis vaccine (as a control for comparison). Ten of the participants received a second dose of the vaccine at day 28. The study’s goal was to analyze the safety and ability of the vaccine to induce an immune response.
Good news: It seems safe!
Thankfully, chimpanzee adenovirus vector vaccines are very well-studied for use against other viruses, and there is a lot of data showing that these vaccines are safe. Consistent with the previous data, the ChAdOx1 nCoV-19 vaccine was well-tolerated with no severe side effects. However, there was a high incidence of mild side effects - study participants most commonly experienced fatigue and headache. Thankfully, the side effects quickly cleared up on their own and administering paracetamol (Tylenol) before the vaccine reduced these symptoms in some participants.
Good news: Induces two strong immune responses!
The vaccine induced neutralizing antibodies against the SARS-CoV-2 spike protein, which increased following a second dose of the vaccine. These antibodies could theoretically find circulating SARS-CoV-2, bind to the spike proteins, and block the virus from entering a human cell (see Figure).
Although it is promising that the ChAdOx1 nCoV-19 induces neutralizing antibodies, recent studies have suggested that SARS-CoV-2 antibodies do not last for an extended period. Thankfully, the ChAdOx1 nCoV-19 vaccine also caused a T cell response against the spike protein, which may be more critical for fighting SARS-CoV-2. Two types of T cells can fight infections - helper and killer T cells. Killer T cells are especially important in viral infections and are named because they “kill” cells infected by a virus .
During a viral infection, an infected cell can break up the virus and present pieces of the virus on its surface. Killer T cells can recognize viral pieces and kill the cell. During a SARS-CoV-2 infection, infected cells can break up the virus and present viral proteins, such as the spike protein, on its surface. Vaccine-induced T cells could then (again, theoretically) kill the infected cells, preventing viral replication and spread (see Figure).
Figure: The ChAdOx1 nCoV-19 vaccine induces neutralizing antibodies and killer T cells against the SARS-CoV-2 spike protein.
SARS-CoV-2 uses its spike protein to gain entry into a human cell, where it hijacks the cell’s machinery to replicate.
Antibodies against the spike protein bind to the spike protein on circulating SARS-CoV-2, which blocks entry into human cells, preventing infection.
Infected cells break down the virus and prevent the spike protein on its surface.
Killer T cells recognize the spike protein and kill the infected cell.
While this is exciting, there are some missing pieces.
It is important to note that this preliminary publication only identified the presence of an antibody and T cell response; the researchers have not yet addressed whether the immune response is protective against COVID-19. However, promising studies have shown that the ChAdOx1 nCoV-19 vaccine is protective in monkeys. So far, the participants have only been followed for 56 days, so there is also no information on how long the immune response is maintained, so we don’t know how long the vaccine will offer protection. Previous studies using chimpanzee adenovirus vaccines have shown a long-term response of at least 1 year, so hopefully, the ChAdOx1 nCoV-19 will be similar. Both of these missing pieces should be addressed soon. The current study will continue for a year to analyze whether the participants that received the ChAdOx1 nCoV-19 are less likely to become ill with COVID-19 and how long the immune responses are maintained.
The phase I/II trial was also limited in its diversity. The study did not include older participants or those with underlying health conditions, and these are the populations where the vaccine is needed the most. Also, 90% of the participants were white, so the vaccine must be evaluated on other ethnicities.
Looking forward.
Thankfully, large scale phase III trials are already underway to address these issues. The trial will be extended to countries with high virus transmission, like Brazil, South Africa, and the US, to analyze the protective capacity. With the high transmission rate currently occurring in these countries, I am hopeful that the necessary data will be acquired relatively quickly.