Investigators aim to assess a vaccine derived from weakened adenovirus in 1100 patients over 2-6 months.
Investigators from the University of Oxford have begun testing a potential vaccine for coronavirus 2019 (COVID-19) in 1100 volunteer patients, and are anticipating results may take 2-6 months.
The first pair of volunteers were split to either investigative vaccine or control on April 23. Investigators will be assessing ChAdOx1 nCoV-19, a vaccine made from the ChAdOx1 virus—a weakened version of the adenovirus shown to cause infections in chimpanzees.
The vaccine is also comprised of genetic material used to make Spike glycoproteins, a surface protein from SARS-CoV-2 that plays an essential role in the virus’ binding to ACE2 inhibitors and eventual infection of the person.
“By vaccinating with ChAdOx1 nCoV-19, we are hoping to make the body recognize and develop an immune response to the Spike protein that will help stop the SARS-CoV-2 virus from entering human cells and therefore prevent infection,” a statement from the University of Oxford read.
ChAdOx1-derived vaccines have been given to 320-plus people to date, according to the university, with consistent reports of safety and tolerability. Temporary adverse events have included raised temperature, headache, and sore arm.
The New York Times reported earlier this week findings from the Rocky Mountain Laboratory in Montana showing that 6 rhesus macaques given the university’s hAdOx1 nCoV-19 vaccine were free of SARS-CoV-2 after 4 weeks of sustained virus exposure.
The Montana-based investigators emphasized the rhesus macaques are “pretty much the closest thing we have to humans,” and that previous test subjects exposed to the test levels of the virus were sick over time.
These promising initial findings, combined with the pressing need of prophylactic measure against the virus, has led to major investment in the candidate. The UK government previously pledged about $25 million to the Oxford trial, and the Serum Institute of India—the world’s largest producer of vaccines—announced intentions to make 40 million doses of hAdOx1 nCov-19 prior to trial results.
Investigators intend to recruit their 1100 participants at multiple study sites across Oxford, Southamptom, Lond, and Bristol, randomizing participants to either vaccine or licensed control vaccine MenACWY—a common adolescent vaccine for group A, C, W, and Y meningococcus administered in the UK since 2015.
The main outcome of the trial is to assess the effectiveness, safety, and immune responses associated with the vaccine against COVID-19, based on a dose established from previous clinical work with other ChAdOx1 vaccines.
Investigators reasoned the active control vaccine will help better interpret participant response to ChAdOx1 nCoV-19—as MenACWY will cause similar early adverse events as the investigative vaccine, assuring absolute blindness to randomization.
“It is critical for this study that participants remain blinded to whether or not they have received the vaccine, as, if they knew, this could affect their health behavior in the community,” the university stated.
Participants are required to be between 18-55 years old, in good health, and cannot have previously tested positive for COVID-19. Pregnant, intending to become pregnant, breastfeeding, or previously adenoviral vaccine-test patients are excluded from the trial.
Investigators intend to expand split, randomized vaccinations from 2 participants on day 1, to 6 on day 3, to eventually greater daily rates after day 5. The initial participants are monitored for 48 hours prior to expanded assessment.
An electronic diary is provided to participants to record symptoms for 7 days following vaccination, as well as any unwell feelings experienced following 21 days. They are required to attend follow-up visits with clinicians to share their status and review notes from diaries. Immune response to the vaccine will be assessed via blood samples.
Because investigators will assess the vaccine’s protection from COVID-19 by comparing the number of infections in the control group with those in the vaccinated group, a portion of participants will be required to develop COVID-19.
Their estimation of results taking 2-6 months is dependent on the rate of community transmission, and how many participants are eventually infected with COVID-19.
Investigators iterated that a great rate of investigative vaccines are not found to be promising before reaching clinical trial stage—and even those that are, may fail at that stage anyway. Regardless of the phase 1 outcomes, they stressed the significance of procuring findings.
“If we are unable to show that the vaccine is protective against the virus, we would review progress, examine alternative approaches, such as using different numbers of doses, and would potentially stop the program.”