CAMBRIDGE, United Kingdom — Good news in the race for a safe and effective vaccine targeting SARS-CoV-2. The latest announcement of clinical trial results comes from a collaboration between the University of Oxford and pharma giant, AstraZeneca. Preliminary findings show that their COVID-19 vaccine, dubbed AZD1222, is safe and well-tolerated in humans. The study also reports that the vaccine induces robust antibody and T cell immune responses in humans.
The AZD1222 vaccine, formerly known as ChAdOx1 nCoV19, was coinvented by the University of Oxford and its spin-out company, Vaccitech. It is based on a type of common cold virus, called adenovirus, that infects chimpanzees. The researchers modified this virus so that it is impossible for it to cause disease in humans. The weakened virus is then used as a vector to deliver the genetic material for the SARS-CoV-2 spike protein into human cells. Using these instructions, the cells can then produce the spike protein in the body in order to present it to the immune system.
The spike protein is the main surface protein of SARS-CoV-2 that controls viral entry into cells. Scientists in vaccine development against COVID-19 believe that this protein is an important target for teaching the human immune response to attack SARS-CoV-2.
“The immune system has two ways of finding and attacking pathogens – antibody and T cell responses,” explains lead study author, Andrew Pollard, Chief Investigator of the Oxford Vaccine Trial at the University of Oxford, in a statement. “This vaccine is intended to induce both, so it can attack the virus when it’s circulating in the body, as well as attacking infected cells. We hope this means the immune system will remember the virus, so that our vaccine will protect people for an extended period.”
Trial methodology
The study is a phase I/II trial of the AZD1222 vaccine that is ongoing across five trial sites in the UK. It has enrolled 1,077 healthy adults, ages 18 to 55, with no history of COVID-19. The overall primary goals of the study are to assess the safety of the vaccine, and to determine whether the vaccine can protect against COVID-19.
The study is randomized and controlled, which means that participants were randomly assigned to receive either the study vaccine or a control vaccine. The trial is also single-blinded, meaning that only the researchers doing the study know which vaccine was administered. This type of study design can help reduce sources of bias.
All participants in the study received either the experimental AZD1222 vaccine against COVID-19 (543 people), or a meningitis vaccine (MenACWY) as a control (534 people). A subset of these participants (56 given the experimental vaccine, and 57 in the control group) were also asked to take the pain killer paracetamol before vaccination and for 24 hours after to help reduce any vaccine-associated reactions.
The study participants are further stratified into four groups, based on sample collection and measurement protocols. Safety and immune responses are being measured in all groups.
Participants in three of the groups (groups 1, 2, and 4) received one dose of the randomly-assigned vaccine. A separate group (group 3) consisted of ten people who all received two doses of the AZD1222 vaccine, administered 28 days apart. This group was unblinded and is being monitored to see if immune responses are stronger after a second dose of vaccine.
No ‘unexpected reactions’ from vaccine
The study results, published this week in the medical journal The Lancet, cover the first 56 days of the vaccine trial. Study participants are expected to be followed-up for at least one year after vaccination to assess the vaccine’s long-term safety and immune response profile.
The study finds the AZD1222 vaccine to be well-tolerated, both as a single and as a double dose. There were no serious adverse events. Fatigue and headache were the most common adverse events, and were reported by 70% of all participants given the AZD1222 vaccine. Other common reactions included injection site pain and tenderness, chills, feverishness, malaise, and muscle ache. Compared to the control vaccine, the AZD1222 vaccine caused a slightly higher frequency of adverse events. However, some of those reactions could be reduced with paracetamol.
“The interim Phase I/II data for our coronavirus vaccine shows that the vaccine did not lead to any unexpected reactions and had a similar safety profile to previous vaccines of this type,” Pollard said in a statement.
Antibody responses after coronavirus vaccine
Much of the focus on SARS-CoV-2 vaccination strategies so far centers around developing a strong antibody response against the virus. Scientists believe that, in order to mount an effective immune response against a viral pathogen like SARS-CoV-2, these antibodies must also be able to neutralize, or block the virus from entering cells.
The study reports that antibody responses against SARS-CoV-2 are detected in the vaccine recipients. A single dose of the AZD1222 vaccine produced a four-fold increase in antibody levels that peaked by day 28 after vaccination, and remained high until the day 56 measurement.
The response was even higher in participants who received the second vaccine dose. Neutralizing antibody responses were seen in 91% of the 35 evaluated participants who received one dose of the AZD1222 vaccine, and in all 10 participants receiving the second dose.
The authors report that pre-vaccination samples from a small number of participants had detectable neutralizing antibodies and T cells against SARS-CoV-2. They noted that these responses were probably due to a past asymptomatic infection.
The team of scientists also looked for another component of the immune response, known as T cells, in the vaccine recipients. T cells are a type of white blood cell that can help coordinate the immune response, and even directly kill virus-infected cells.
The study reports that T cells targeting the SARS-CoV-2 spike protein are present in all 43 evaluated participants in the study. This response peaked at 14 days after vaccination and declined slightly at the day 56 measurement. A second dose of vaccine does not show an increase of the response.
Two doses of COVID-19 vaccine better than one?
“The immune responses observed following vaccination are in line with what we expect will be associated with protection against the SARS-CoV-2 virus,” Pollard notes, “although we must continue with our rigorous clinical trial program to confirm this. We saw the strongest immune response in participants who received two doses of the vaccine, indicating that this might be a good strategy for vaccination.”
The authors also point out some limitations of their study. That’s especially with regard to a need for the inclusion of older age groups, people with comorbidities, and ethnically and geographically diverse populations. Many of these groups will be part of the phase II and III trials of the vaccine that are currently underway in the UK, Brazil, and South Africa, and are due to start in the US.
“We are encouraged by the Phase I/II interim data showing AZD1222 was capable of generating a rapid antibody and T-cell response against SARS-CoV-2,” says Mene Pangalos, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca. “While there is more work to be done, today’s data increases our confidence that the vaccine will work and allows us to continue our plans to manufacture the vaccine at scale for broad and equitable access around the world.”