Oxford Vaccine Prompts Immune Response

August 30, 2020

A leading coronavirus vaccine candidate has shown promise in early trials, triggering participants to build up immune cells against the virus without causing any serious reactions, according to results released today.

The vaccine, called ChAdOx1 nCoV-19, was developed at the University of Oxford in the UK and consists of a weakened version of a common cold virus known as adenovirus that infects chimpanzees, Live Science previously reported. According to the new study, the team genetically modified the virus so that it cannot replicate and grow in humans, and they added genes that code for so-called “spike” proteins, which the coronavirus uses to infect human cells. The idea is that the vaccine would teach human immune cells to recognize the spike protein, so if a person is exposed to the coronavirus, their immune system can destroy it.

The Oxford University team began testing the vaccine on humans in April and published early results from their Phase 1 and still ongoing Phase 2 trials today (July 20) in the journal The Lancet. During these two early phases, the researchers tested the safety and immune response to the vaccine on a total of 1,077 participants with no history of COVID-19 between the ages of 18 and 55 at five hospitals in the UK.

Half of the participants received a candidate vaccine and half received a control vaccine against meningococcal bacteria. The meningococcal vaccine served as a control, making it impossible for participants to guess whether they received the actual vaccine or control, as both could cause similar side effects. Participants had blood samples taken on the day they received the vaccine and 28 days later; they will also be followed up at 184 and 364 days after they first received the vaccine, according to the study. Safety and immune response were assessed in all participants who received ChAdOx1 nCoV-19, but some had additional blood drawn to measure their immune response in more detail. A small group of participants also received a second dose of the vaccine.

The researchers found that the vaccine did not cause any serious adverse events, but it did prompt some mild side effects, including fatigue, fever, headache, pain at the injection site, muscle pain, and chills. A subset of the participants were asked to take paracetamol (acetaminophen, a brand in Tylenol) before and every 6 hours for 24 hours after the vaccine. These participants showed fewer mild side effects.

The team found that the experimental vaccine produced neutralizing antibodies – or antibodies that not only latch on to the virus but also prevent it from infecting cells – 91 percent of participants (32 of 35 tested) received a single dose of the vaccine and 100 percent of those received two doses. The vaccine also boosted levels of T cells that recognize SARS-CoV-2. T cells are a group of white blood cells that may either directly kill the virus or step up the rest of the immune response to fight it.

“There is still much work to be done before we can confirm whether our vaccine will help manage the COVID-19 pandemic, but these early results are promising,” co-author Sarah Gilbert, a professor of vaccinology at the University of Oxford, said in a statement.” In addition to continuing to test our vaccine in phase 3 trials, we need to learn more about the virus – for example, we still don’t know how strong of an immune response we need to provoke to effectively prevent SARS-CoV-2 infection.” (According to Bloomberg News, Gilbert’s three children, 21-year-old triplets, are participating in a clinical trial).

The authors also note that more studies are needed to replicate the results in different populations (91 percent of the trial participants were white, with an average age of 35). The team will follow these participants for at least a year, the statement said, but is also currently recruiting volunteers for ongoing phase 2 and 3 trials in the UK, Brazil and South Africa.

Today, Chinese researchers also reported similar results for another experimental vaccine, also based on a weakened adenovirus, in The Lancet. This team used an adenovirus that normally infects humans, not chimpanzees. The new study also found no serious adverse events. In their phase 2 trial, more than 90 percent of participants developed a T-cell response and about 85 percent developed neutralizing antibodies.

“The results of these two studies bode well for the phase 3 trial, and the vaccine must be tested in a larger population of participants to assess its effectiveness and safety,” wrote Naor Bar-Zeev and William J Moss of the Johns Hopkins International Center for Vaccine Access in an accompanying commentary in “The Lancet.” Overall, the results of the two trials were broadly similar and very promising.”

The University of Oxford is continuing to study the vaccine candidate in its ongoing Phase 2 and larger Phase 3 trials, and has partnered with AstraZeneca to mass-produce doses of the virus. According to The Guardian, the team is also planning to begin the long-debated challenge study – in which they would deliberately expose healthy volunteers to the coronavirus after they’ve been vaccinated with the experimental vaccine – in a few months to coincide with their phase 3 trial, or after their phase 3 trial has been completed.

The Oxford vaccine is one of nearly 200 candidate vaccines being developed worldwide to prevent infection with the new coronavirus. Last week, US biotech company Moderna, in collaboration with the National Institutes of Health, also published promising early results from a Phase 1 trial of its vaccine candidate in the New England Journal of Medicine. The vaccine also appears to be safe, well-tolerated, and encourages the production of neutralizing antibodies, according to a previous report by Live Science.