The foot race to develop the first effective vaccine against COVID-19 involves an awfully crowded field, with 137 candidate vaccines in pre-clinical study worldwide and another 23 actually in development. But a leader seemed to emerge today with research published in the Lancet reporting promising results in a robust study by investigators at Oxford University in England.
The study began in April, with a sample group of 1,077 adults aged 18 to 55—an age group young enough to tolerate exposure to SARS-CoV2, the virus that causes COVID-19, with less risk of adverse effects than would be seen in older, more vulnerable adults. The group was divided more or less in half, with 543 participants receiving the experimental COVID-19 vaccine, and the other 534 serving as a control group, receiving an existing vaccine against meningococcal vaccine. (The investigators chose not to use an inert saline solution for the control group because both vaccines can cause side effects such as achiness, fever and fatigue. Saline would cause no such symptoms and would thus reveal which group was the control group and which was not.)
The vaccine uses a harmless-to-humans chimpanzee adenovirus as a delivery vector. That virus is modified to carry spike proteins from SARS-CoV-2—the component of the coronavirus that, in theory, should induce the sought-after immune response in humans. What the researchers were looking for were two kinds of immune reaction: humoral immunity, or the system-wide generation of antibodies against the virus; and cellular immunity, or the activation of immune system T-cells that attack human cells infected with the COVID-19 virus.
They very much got what they were looking for. T-cell responses to the vaccine became detectable by day seven after the injection of the vaccine, peaked at day 14 and remained elevated at least until day 56. Humoral antibodies peaked at day 28 and also remained elevated at least until day 56. That eight-week mark is a good early measure of a vaccine’s efficacy and ability to confer at least short-term immunity
“We are seeing good immune responses in almost everybody,” Dr. Adrian Hill, a professor of human genetics at Oxford University and one of the researchers on this particular study, told the Associated Press. “What this vaccine does particularly well is trigger both arms of the immune system.”
It actually does even more than that—if more of the vaccine is administered. Of the 1,077 subjects, a handful, just 10, were selected for a second booster dose on day 28, when they were still in the midst of their first-dose immunity. That small sample group kept the risk of overexposure limited to just a few subjects. When the antibodies of 37 of the subjects who had received a single dose were tested against the virus in vitro—or in a test tube—23 of them, or 62%, completely neutralized the virus as late as day 56. When the same study was conducted in vitro with the 10 subjects who had received a second dose, the neutralizing effect was a perfect 100%.
The vaccine, for all its promise, is not yet ready for prime time. Phase 2 and phase 3 trials must still be conducted, with much larger sample groups including people who have or have had COVID-19 already. In addition, while using a relatively young sample group was wise in terms of safety, the vaccine still must be tested in older individuals who, after all, are at much higher risk for complications and death as a result of COVID-19 and are the group most in need of an effective vaccine.
Some of those trials are already underway. One study of the vaccine involving a sample group of 3,000 people began in Brazil in June. A similar trial began in South Africa at the same time. A bigger study of 30,000 people in the U.S. is still to come, and planned to start later this summer.
But even these early results are encouraging enough to help vindicate the decision of Cambridge-based pharmaceutical giant AstraZeneca to partner with Oxford. The company has committed to mass producing 2 billion doses of a successful vaccine as soon as it’s perfected.
Oxford is by no means alone. Of the 23 vaccines currently in development, another, by Massachusetts-based Moderna Inc., in collaboration with the U.S. National Institutes of Health, is also racing ahead of the pack. In a phase 1 study released last week, 45 subjects who received the sample vaccine produced antibodies that neutralized SARS-CoV-2 in vitro as effectively as antibodies produced by people who had actually had the disease. New York-based Pfizer pharmaceuticals is developing its own vaccine in a Phase I/II trial—which tests safety, effectiveness, side effects and dosing and ideal dosing level—has similarly shown promising results, with the U.K. already lining up to buy 90 million doses once it is approved.
The Oxford study, the largest of its kind, does bring us a significant step closer to the release of a vaccine—or a whole arsenal of vaccines—against the COVID-19 pandemic. But we’re not there yet. For now, the disease still rages—and the world still waits.
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Contributor: Jeffrey Kluger