Initial human trial results for a promising COVID-19 vaccine have been published in the journal The Lancet. The vaccine, developed at Oxford University, has so far been found to be safe and induce the two key immune responses needed to protect against coronavirus infection.

The Oxford COVID-19 vaccine, recently renamed from ChAdOx1 nCoV-19 to AZD1222, was developed incredibly rapidly, with Phase 1/2 human trials starting in April. The newly published preliminary data reports the results of a blind, randomized controlled trial testing the safety and immunogenicity of the experimental vaccine in 1000 subjects.

The cohort blindly received either AZD1222 or a meningococcal vaccine as control. The initial phases of human testing in a vaccine trial are designed to investigate how safe the new vaccine is and whether it triggers biomarkers associated with an effective immune response.

The data suggests the vaccine causes no serious adverse effects, although more than half of subjects did display mild to moderate side effects, including injection site pain, fever and fatigue. All these adverse effects resolved within 48 hours of treatment.

Looking at immune responses, the vaccine generated robust antibody and T-cell responses in all subjects with neutralizing antibodies detected in 91 percent of subjects one month after a single dose of the vaccine. A small cohort receiving a booster dose one month after the initial dose showed even stronger antibody responses.

T-cell responses were seen to peak around two weeks after a single dose of the vaccine. At the two-month follow-up those T-cell levels were seen to slightly decline. It is unclear at this stage what kind of long-term immunity the vaccine could confer, however, these two immune biomarkers induced by the vaccine are similar to what is seen in recovered COVID-19 patients.

“The immune system has two ways of finding and attacking pathogens – antibody and T cell responses,” explains Andrew Pollard, lead author on the new study. “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.”

Researchers not affiliated with the Oxford vaccine are expressing cautious optimism after reviewing these new data. Although these results present exactly what one would hope to see at this stage in the development of a successful vaccine it is important to note it is too early to know whether this leads to protection from infection in the real world.

“The preliminary findings look very promising with responses to the vaccine similar to what is seen post-natural infection,” says Beate Kampmann, from the London School of Hygiene and Tropical Medicine. “Whether this is what’s needed to protect against infection and/or disease cannot be established with these early-phase datasets.”

Oxford has joined forces with pharmaceutical company AstraZeneca to expand testing and lay the groundwork for mass manufacturing of the vaccine. A number of large-scale Phase 3 trials are already underway with tens of thousands of people enrolled across the UK, US, Brazil, and South Africa. Over the next few months, it’s hoped these larger will deliver insights into how protective the vaccine actually is in real-world conditions.

Phase 3 vaccine trials generally take quite a long time. This is because researchers must recruit a cohort of subjects deemed to be at a high risk of contracting whatever disease is targeted by the vaccine, and then follow those subjects for months as they inhabit the real world. After a period of time, the researchers can then compare the number of infections between the vaccine and placebo groups to determine what real-world efficacy the vaccine has in protecting a person from infection.

Testing a vaccine by deliberately exposing healthy volunteers to a pathogen is known as a human challenge trial. There has been a significant debate amongst scientists for several months over whether human challenge trials should be conducted to speed up the testing of COVID-19 vaccines.

A recent open letter directed to Francis Collins, director of the National Institutes of Health, called for broad deployment of human challenge trials for COVID-19 vaccine development. Co-signed by over 100 academics, scientists, and medical ethicists, the letter lays out several principles for safety oversight in this type of clinical trial.

Several members of the Oxford vaccine research team are also calling for human challenge trials to be run in parallel with the ongoing Phase 3 trials already underway. It has been reported that some Oxford scientists have already begun internal preparations for a human challenge trial that could commence later this year.

The new study was published in the journal The Lancet.

The Phase 3 trial will recruit 30,000 participants in the US, with half to receive the vaccine at 100 microgram dose levels, and the other half to receive a placebo.

It is designed to show whether the vaccine is safe and can prevent infection by the SARS-CoV-2 virus, or if people still get infected whether it can prevent the infection from progressing toward symptoms.

If they do get symptoms, the vaccine can still be considered a success if it stops severe cases of COVID-19.

The study should run until October 27, according to its page on clinicaltrials.gov.

The announcement came after the New England Journal of Medicine on Tuesday published results from the first stage of Moderna’s vaccine trial, which showed the first 45 participants all developed antibodies to the virus.

Moderna, currently in the middle stage, is considered to be in a leading position in the global race to find a vaccine against the coronavirus, which has infected more than 13.2 million people and killed 570,000.

China’s SinoVac is also at Phase 2.

Russian news agency TASS on Sunday announced Russian researchers have completed clinical trials on a vaccine, though they have not shared their data.

Scientists caution that the first vaccines to come to the market may not be the most effective or safest.

Moderna had previously published “interim results” from the first stages of its trial, called Phase 1, in a press release on its website in May.

These revealed the vaccine had generated immune responses in eight patients, a result called “encouraging” by Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases, which is co-developing the vaccine.

But some in the scientific community said they would reserve judgment until they saw the full results in peer-reviewed form.

According to the new paper, 45 participants were split into three groups of 15 each to test doses of 25 micrograms, 100 micrograms, and 250 micrograms.

They were given a second dose of the same amount 28 days later.

After the first round, antibody levels were found to be higher with higher doses.

Following the second round, participants had higher levels of antibodies than most patients who have had COVID-19 and gone on to generate their own antibodies.

More than half of the participants experienced mild or moderate side effects, which is considered normal.

The side effects included fatigue, chills, headache, body ache, and pain at the injection site.

Three participants did not receive their second dose.

They included one who developed a skin rash on both legs and two who missed their window because they had COVID-19 symptoms, but their tests later returned negative.

“The results look pretty good and look pretty consistent,” David Lo, a professor of biomedical sciences at the University of California Riverside told AFP.

But he cautioned that more work was needed to evaluate the vaccine’s safety including making sure that it did not backfire by eventually making the immune system “tolerant” toward the real virus.

Amesh Adalja, an infectious disease specialist at Johns Hopkins University, added it was encouraging that the participants developed high levels of an advanced class of antibodies.

He added, however: “You have to be very limited in how much you can extrapolate from a phase one clinical trial because you want to see how this works when a person is exposed to the actual virus.”

The Moderna vaccine belongs to a new class of vaccine that uses genetic material in the form of RNA to encode the information needed to grow the virus’s spike protein inside the human body, in order to trigger an immune response.

The spike protein is a part of the virus that it uses to invade human cells, but by itself, the protein is relatively harmless.

The advantage of this technology is that it bypasses the need to manufacture viral proteins in the lab, shaving months off the standardization process, and helping to ramp up mass production.

No vaccines based on this platform have previously received regulatory approval.

Following favorable results in trials on primates, the next step is to manufacture doses for human trials, said Kiat Ruxrungtham, director of the Bangkok’s Chulalongkorn University vaccine development program, Reuters reported.

“At first we were going to send them in June, but it was not easy to plan everything,” Kiat told a news conference.

There are no approved vaccines for the virus that causes COVID-19, but 19 candidates are being trailed in humans globally. China is leading the race, with an experimental vaccine by Sinovac Biotech Ltd.

Thailand’s first facility should complete production in October and send the products to a second facility, which should finish by November, he said. Originally the earliest target was September, but Kiat said not enough vaccine can be ready by then.

Facilities in San Diego and Vancouver will produce 10,000 doses for the trials for 5,000 people. The first group, aged 18 to 60, will receive different doses of the vaccine, he said.

The trials will not accept volunteers “until we receive approval from the Thai Food and Drug Administration and an ethics committee,” Kiat said.

Thai company BioNet-Asia is preparing its facilities for large-scale manufacturing if the trials prove successful, he said.

“If everything goes according to plan, the coronavirus vaccine will be ready for Thailand in the third or fourth quarter next year,” Kiat said.

Thailand on Sunday had a total of 3,217 confirmed infections, with no local transmissions reported in over a month, and 58 COVID-19 deaths.