In a race against time, coronavirus vaccine testing expands

Tribune Content Agency

SAN JOSE, Calif. — In the battle to prevent COVID-19 infection, a vaccine will be our safest armor.

As casualties climb, pharmaceutical companies and young volunteers are racing to design, build and test a defense that can protect us. Unless a vaccine is developed soon, people susceptible to the virus will continue to be at risk.

Human testing has begun of six potential vaccines in an effort to prove that they’re safe and can produce an immune response. Over 70 more are being reviewed for safety and effectiveness in preparation for human testing. In promising news, this week Chinese researchers reported that one candidate has already proven its usefulness in animals, protecting monkeys from infection.

Meanwhile, more than 3,200 young volunteers from 52 nations have enlisted to speed up research, registering with the nonprofit 1DaySooner.org to be vaccinated and then deliberately exposed to the virus in the final phase of testing, so scientists can more quickly learn if this armor works.

“If it accelerates vaccine development by a month, that prevents hundreds of thousands of infections, saving lives,” said Carson Poltorack, 23, a Stanford graduate soon to pursue dual MD/PhD degrees at the University of Pennsylvania. Young and healthy, he signed up to volunteer because “I would much rather be the one shot at — I have a far lower chance of dying or having a serious outcome than other groups.”

Despite these efforts, the battle will be neither simple nor fast. Determining a vaccine’s safety and effectiveness takes time, said experts.

The process will take a year to a year and a half, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, in early March. Other experts think it will take even longer.

Until a vaccine is developed, it’s likely that there will be a new wave of infections when stay-at-home orders are eased. People at high risk of developing COVID-19 — including those over 65 or with underlying medical conditions — will again be vulnerable to infection by the potentially deadly disease.

Vaccines are important because the human body responds to infection too slowly to protect itself.

When a person is exposed, their immune system launches a defense. It responds by generating antibodies that specifically recognize proteins from the virus, called SARS-CoV-2. These antibodies trigger white blood cells that eliminate the virus.

But by the time these immune cells are ready, the virus has already taken over host cells. It’s too late.

A person is protected from future infection only after recovery. So-called “memory cells” prompt a faster immune response the next time SARS-CoV-2 invades their body.

Vaccines work by triggering production of these antibodies and memory cells — without forcing a person to suffer through the illness.

One approach, used by the Massachusetts biotech company Moderna, introduces a spike-shaped protein found on the surface of SARS-CoV-2, which could put our immune systems on alert without actually giving us the disease. A second round of tests is being conducted at Kaiser Permanente Washington Health Research Institute in Seattle, suggesting there were no adverse effects so far.

Another approach, used by China-based Sinovac Biotech and others, uses an inactivated form of the virus, which could prime our immune systems without the consequences of COVID-19. Seven days after monkeys vaccinated by Sinovac were exposed to the virus, it could not be detected in their bodies, according to a report published April 19 on the preprint server bioRxiv. But only eight monkeys were tested, and they don’t develop the most severe symptoms the virus causes in humans

It might sound straightforward, but vaccine development can take years because the candidates must be proven safe and effective through multiple phases of testing.

According to the U.S. Food and Drug Administration, the typical timeline goes like this: Phase 1 trials, which assess the safety of a vaccine, take at least a few months; phase 2 trials, which test efficacy in hundreds of people, take a few months to two years and phase 3 trials, which involve randomized and “blind” testing in several hundred to several thousand patients to better reveal the effectiveness, benefit and possible adverse reactions in diverse populations, take one to four years. Ervebo, the first federally approved vaccine for the Ebola virus, was approved in late 2019 — after five years of clinical trials.

“What takes so long is not so much the science part of building the vaccine; it’s the safety testing in enough people over enough time,” said Gregory Poland, director of the vaccine research group at the Mayo Clinic, in an interview with the Journal of the American Medical Association.

What could go wrong? One major concern is that vaccine-induced antibodies could make disease progression worse upon exposure to the actual virus. Scientists have previously seen this effect in animal testing for related coronaviruses.

The potential vaccine also needs to show that it provokes an immune response, leading to antibody production.

The companies with potential vaccines entering clinical trials are taking different approaches, each with the hope that theirs works. While some have been tested in animals and shown an immune response, others are skipping animal testing due to the urgency of the need. With every day of delay, hundreds of Americans sicken.

“With this specific strain of coronavirus, nobody’s knowledge is greater than 12 weeks old,” said Poland in March.

This week, 35 members of the House of Representatives sent a letter to the FDA and U.S. Department of Health and Human Services urging them to speed up the evaluation and approval process for a COVID-19 vaccine and to prepare for a more rapid deployment to the public.

They also urge an alternative to traditional Phase 3 of testing. In addition to taking the usual route — vaccinating people and then waiting to see if natural infection rates are lower — they propose “challenge trials” which deliberately expose vaccinated volunteers to the virus. This would provide important data more quickly, which could give manufacturing a head start.

“It’s a sacrifice for the greater good,” said Josh Morrison, founder of the 1DaySooner “challenge trials” recruitment site. The group limits volunteers to those under age 45 with no underlying health conditions; the COVID-19 fatality rate in that group is under 0.2%. Still working out the details, it hopes to be up and running within five months. Volunteers will be screened and carefully selected, then offered to research teams.

Sophie Rose, 22, a Stanford graduate who will study at the Johns Hopkins School of Public Health, has volunteered to receive a COVID-19 vaccine.

Volunteer Sophie Rose, 22, a Stanford graduate with an interest in biosecurity and infectious disease, said “the risk of getting extremely sick is certainly something I’ve considered carefully — and am OK with because of the access to medical care that volunteers would be afforded.”

Will immunity last? What we know about similar coronaviruses highlights potential challenges. There’s no long-term immunity in people infected by other coronaviruses that cause symptoms similar to the common cold. Antibody levels in people infected with SARS-CoV-1 and MERS-CoV are initially weak or decrease after a few years.

Finally, even if a potential vaccine proves effective, another challenge will be scaling up production to manufacture enough vaccines for the entire population.

To speed up the process, HHS is working with companies to not only prepare for later-phase clinical trials in parallel but also provide funding for manufacturing. This support comes from the Biomedical Advanced Research and Development Authority, whose director, Rick Bright, stepped down earlier this week.

“We’re trying to do something really hard,” said Morrison. “The best minds are working on it.”

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