Oxford, CanSino Covid-19 vaccines: Trial results reveal 2 major breakthroughs

The results are starting to flood in from the coronavirus vaccine candidates that piqued our interest back in spring. There are now three vaccines in the third and largest stage of human trials.

On July 14, Moderna Inc. released the results of its coronavirus vaccine candidate, showing that it was able to induce an immune response in all participants. On Monday, we received the results of two other much-awaited vaccine candidates:

• ChAdOx1 nCoV-19, a viral vector vaccine created by University of Oxford scientists
• Ad-nCov, a viral vector vaccine made by Chinese biotech company CanSino Biologics

With the release of these two vaccines in tandem with the Moderna vaccine, historic efforts that began in March are beginning to yield results.

Both the Oxford and CanSino trials produced two results crucial for their future success: The vaccines trigger immune system supportive T-cells, and they appear to be very safe.

These trials still leave questions unanswered for those who may need a vaccine the most.

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The Oxford vaccine — This vaccine first made headlines in April, when macaques who received the vaccine and a dose of the coronavirus managed to stay healthy for 28 days. Now, a paper published in The Lancet reveals results from 543 adults who were given The Oxford Vaccine (ChAdOx)and 534 who were given a meningococcal vaccine. Ten participants also got booster shots.

After 14 days, between 91 and 100 percent of those who got the Oxford coronavirus vaccine produced neutralizing antibodies. These are the gold standard of antibodies that stop the virus from infecting healthy cells. All of those in the booster group also had neutralizing antibodies.

The CanSino vaccine — This vaccine has also been moving very quickly – that candidate first made headlines in May when a small trial on humans demonstrated that the vaccine could invoke immune responses in 108 people. A paper also published Monday in The Lancet updates those findings, revealing how subjects who got two doses faired.

Fifty-nine percent of the 253 people in the higher dosage group produced neutralizing antibodies 28 days post-vaccination. In the lower dosage group, 47 percent of 129 participants produced neutralizing antibodies. These responses were detected 28 days after just one round of vaccination.

While the Oxford Vaccine's results are on a slightly larger scale than CanSino's, the two vaccines are similar: Both use viral vectors (adenoviruses) to deliver the bits of coronavirus that the body will learn to fight off. By comparison, the Moderna vaccine uses mRNA to train the body to recognizes the viruses' genetic material.

What these vaccines mean for immunity — Scientists are interested in cultivating types of immune responses that don't depend on antibodies, an endeavor in part spurred by preliminary research that suggests antibody levels may wane over time.

This puts a focus on T-cells, which help the immune system remember a pathogen and mount a response.

The CanSino results and the Oxford vaccine results reveal a two-layered immune response in their participants that include both antibodies and T-cells.

• For the Oxford vaccine, T-cells that recognize the spike protein peaked about 14 days after vaccination in 43 participants (the booster dose didn't increase those T-cell levels).
• For the CanSino vaccine, T-cells were also observed in both the high and low-dosage groups within 28 days.

The Moderna vaccine also triggered a T-cell-based response after a second dose, but the levels were "low," the authors reported.

Together, the results suggest that these vaccines likely have more than one way to help our bodies remember the coronavirus — a reality that might soften the blow if antibodies truly do wane over time.

Do these vaccines cause side-effects? — We also know that younger, healthy people seem to fair well when vaccinated. In both studies, the primary group of people tested was healthy adults, aged 18 to 55. These participants reported mild to moderate side-effects from the vaccines, including fever, fatigue, and injection site pain.

For the CanSino vaccine, 72 percent of people in the high dose group had these adverse effects, as did 74 percent in the low dose group.

For the Oxford vaccine, the most commonly reported side-effect was a headache, seen in 70 percent of those who received the vaccine. Participants also reported muscle fatigue, chills, or malaise. When participants received paracetamol (a painkiller) 24 hours after vaccination, those side-effects were significantly reduced, suggesting symptoms can be managed.

What these results can't tell us –  Crucially, these results still can't tell us whether any vaccine can prevent Covid-19 in practice. They only tell us that the vaccine is relatively well-tolerated and can invoke an immune response. We are still playing "the waiting game," says Andrew Pollard, an investigator on the Oxford team.

We also don't know how well these vaccines will be tolerated in specific groups of people most in need.

The Oxford vaccine is designed with the hope that it will be well-tolerated in people with underlying health conditions and the elderly. The Jenner Institute — the group behind the Oxford vaccine — selected their Chimpanzee adenovirus method of vaccination because it can induce a strong immune response after one dose, limiting chances of adverse events in those vulnerable populations.

"This also makes it safer to give to children, the elderly, and anyone with a pre-existing condition such as diabetes," its website notes.

However, the trial of the vaccine was focused on people between the ages of 18 and 55. For now, it can't address that question fully, even though one dose did appear to work effectively in the younger age groups.

The CanSino vaccine trial provides more context on how this vaccine might affect older people: A small subgroup of 65 people who were older than 55 saw less dramatic immune-responses invoked by the vaccine. They also had higher tolerability to the vaccine, experiencing fewer side effects.

That suggests that, in the next round of trials, some people in that age group will receive two doses of the vaccine, the authors note.

What comes next ? –  What matters for all three vaccines is how well they will fare in Phase III clinical trials – the third and largest stage of human testing.

The Oxford Vaccine is already in Phase III trials in the UK, Brazil, South Africa, and the United States – places the coronavirus is still spiking. The CanSino Vaccine is also slated to enter Phase III trials in Brazil. The Moderna vaccine will be tested in United States coronavirus hot spots.

Soon it will become clear which ones work, and what niches each vaccine may be able to fill.