COVID-19 vaccines are moving toward clinical trials

Drug developers are moving their experimental vaccines for COVID-19 into clinical trials at a frenetic pace. Trials for five such vaccines have begun in China. Two are being tested in the US, with a third slated to start this month. And trials of two more are due to begin in the UK and Australia in the coming weeks.

“Everything from basic science to clinical science is progressing at a pace faster than ever before—and very appropriately given the grave nature of the current global crisis,” says Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and Harvard University School of Medicine.

The World Health Organization says at least 70 COVID-19 vaccines are in development, while scientists at the Coalition for Epidemic Preparedness Innovations (CEPI) have counted 115.

Moderna was the first to begin clinical testing of a COVID-19 vaccine, just 66 days after downloading the genetic sequence of SARS-CoV-2. The biotech firm hopes its vaccine will teach the immune system to recognize, seek, and destroy the SARS-CoV-2 spike protein, which the virus uses to infect human cells.

On April 16 Moderna announced receiving a commitment of up to $483 million from the US Biomedical Advanced Research and Development Authority to speed development of the vaccine. The firm said it will hire up to 150 employees in the US this year, including staff to support a round-the-clock production scale-up. Moderna has already begun manufacturing mRNA for use in its potential Phase II and III clinical trials before Phase I has finished. Phase III could begin as soon as this fall.

Most vaccine developers are pursuing this same strategy but using different technologies to achieve it. Moderna encodes genetic instructions for making the spike protein in messenger RNA (mRNA). CanSino Biologics, which began a clinical trial in China in March, encodes the spike in a genetically engineered common cold virus, called an adenoviral vector vaccine. And Inovio Pharmaceuticals, which began a clinical trial in the US in April, encodes the spike in a circular piece of DNA.

All three companies were able to move fast because their vaccines rely on our own cells to produce viral spike proteins with a set of genetic instructions. Yet Inovio and Moderna have never made a commercial vaccine before, prompting some experts to also call for COVID-19 vaccines developed using tried-and-true, albeit slower, approaches.

Sanofi has a plan to fill that need. The company is making a COVID-19 vaccine based on SARS-CoV-2 spike proteins produced in genetically engineered insect cells—the same process it uses for its commercial influenza vaccine, FluBlok. On April 14, GlaxoSmithKline joined arms with Sanofi and pledged to provide its vaccine adjuvant, AS03, which contains molecules that excite the immune system and boost vaccine potency. Clinical trials will start later this year, and the firms hope to have a vaccine available in the second half of 2021.

It’s the first time two big pharma firms have joined to develop a COVID-19 vaccine. Upon hearing the news, stock analysts at SVB Leerink wrote, “Finally, Collaboration!” In their note to investors, they called the collaboration “one of the more promising vaccine programs on the horizon,” since it is backed by two of the largest vaccine developers. Plus, unlike DNA and mRNA vaccines, the technology is already the backbone of an approved vaccine. The analysts are skeptical about the ambitious timeline, however.

Several clinical trials have recently begun in China. Sinovac Research and Development and China National Pharmaceutical Group are both testing vaccines that use inactivated SARS-CoV-2. The Shenzhen Genoimmune Medical Institute has begun clinical trials of two vaccines based on immune cells that are genetically modified to target the SARS-CoV-2 spike protein. And CanSino said it is gearing up for a Phase II study of its vaccine, which could provide evidence that the approach is working.

In the UK, the University of Oxford is preparing to begin a clinical trial of 500 people this month. Half will receive its adenoviral vector vaccine, and half will receive a placebo. Johnson & Johnson is working on its own adenoviral vector vaccine with Barouch’s lab at Harvard and the US government, with a clinical trial slated to start by September.

At least five more mRNA vaccines are set to enter clinical testing this year. BioNTech and Pfizer plan to start their trial by the end of April. Separately, Novavax says it will start clinical trials of its nanoparticle-based vaccine in Australia in mid-May.

On April 9, the World Health Organization announced that it is planning an international study, the SOLIDARITY vaccine trial, which will assess and compare multiple COVID-19 vaccines with each other and a single placebo arm.

CEPI has provided funding to several COVID-19 vaccine front-runners, including the newcomers Inovio and Moderna. In an editorial in the New England Journal of Medicine, CEPI leaders acknowledged there’s no guarantee these firms can scale-up manufacturing to make enough vaccines in time. “It’s therefore critical that vaccines also be developed using tried-and-true methods, even if they may take longer to enter clinical trials or to result in large numbers of doses,” they write.