Vaccines that can protect against many coronaviruses could prevent another pandemic - Science Magazine

A pancoronavirus vaccine might contain a nanoparticle carrier (gray) that holds several different versions of the viral spike protein (other colors).

In November 2020, the agency solicited applications for “emergency awards” to pursue pancoronavirus vaccine development.

And in March, the Coalition for Epidemic Preparedness Innovations (CEPI), an international nonprofit launched in 2017, announced it would spend up to $200 million on a new program to accelerate the creation of vaccines against beta coronaviruses, a family that now includes SARS-CoV-2.

Beyond bats, coronaviruses infect camels, birds, cats, horses, mink, pigs, rabbits, pangolins, and other animals from which they could jump into human populations with little to no immunity, as most researchers suspect SARS-CoV-2 did.

The agency has not given out any of its new awards yet, but Ward’s lab is already pursuing a vaccine targeting a subset of beta coronaviruses.

Their approaches include novel nanocages arrayed with viral particles, the cutting-edge messenger RNA (mRNA) technique at the heart of proven COVID-19 vaccines, and cocktails of inactivated viruses, the mainstay of past vaccines.

Despite the many unknowns, the rapid success of vaccines against SARS-CoV-2 has sparked optimism.

NIAID’s Barney Graham, who helped develop Moderna’s mRNA COVID-19 vaccine, shares the optimism about pancoronavirus vaccines.

Earlier this year, Hannah Turner, a technician at Scripps Research who works with Ward, took a cold, hard look at a now infamous protein: SARS-CoV-2’s spike, which enables the virus to infect cells and is at the heart of several successful COVID-19 vaccines.

All coronaviruses have these spikes, which create the distinctive crownlike appearance that earned them their name, and most pancoronavirus vaccine efforts aim to rouse an immune response to some part of the spike protein.

On this February morning, Turner mixes labmade copies of the SARS-CoV-2 spike with “broadly neutralizing” antibodies harvested from COVID-19 patients.

These antibodies powerfully prevent multiple variants of SARS-CoV-2, as well as the original SARS virus, SARS-CoV, from infecting susceptible cells in test tube studies.

Several strategies for these pancoronavirus vaccines focus on spike, the surface protein common to all members of the viral family.

An ideal pancoronavirus vaccine would protect us from all four of its genera—alpha, beta, gamma, and delta—but most researchers have more modest goals.

Bjorkman and co-workers chose a portion of spike from a range of beta coronaviruses: SARS-CoV and SARS-CoV-2, a virus isolated from a pangolin, and five bat viruses.

Graham, who worked on pancoronavirus vaccines even before the pandemic, reasons that the whole trimer of spike might stimulate better or broader immune protection than just the RBDs.

His team has taken spike trimers from SARS-CoV-2 and two beta coronaviruses that cause human colds and placed them in malleable nanocages, made from two different proteins developed by computational biologist Neil King of the University of Washington (UW), Seattle.

In a third strategy, Graham envisions giving people a series of vaccines, each one containing trimers from a different member of the beta genus, to create a broad defense against the viruses.

Structural biologist Andrew Ward studies the nooks and crannies of a coronavirus spike protein for features common to spikes in other members of the virus family.

A few years ago, McLellan developed a vaccine from the S2 of the MERS virus that protects mice from the virus as effectively as vaccines that feature the full spike.

The antibodies produced by the vaccine also bind to, but do not neutralize, SARS-CoV, SARS-CoV-2, and a human cold beta coronavirus.

McLellan’s lab is now conducting cryo-EM of antibody-stem conjugates, using S2 from SARS-CoV-2, to develop a vaccine for beta coronaviruses.

Although the antibody binds to the RBDs of spike of each virus, it does not block them from attaching to ACE2, cryo-EM showed.

She hopes to initially combine this T cell approach with a B cell strategy that would protect against all SARS-CoV-2 variants.

NIAID’s veteran flu researchers Matthew Memoli and Jeffery Taubenberger want to combine inactivated versions of representative coronaviruses from the four known lineages in the beta genus?

Vaccines based on the entire virus help the immune system take “multiple shots at the target,” Memoli explains, rather than focusing all the responses on spike or bits of it.

How can developers of pancoronavirus vaccines prove their shots protect against a hypothetical SARS-CoV-3.

government considers SARS-CoV, MERS, and many coronaviruses to be “select agents,” subjecting labs that handle them to greater restrictions.

A pancoronavirus vaccine might establish its bona fides under that rule if it works in mice or monkey challenge studies against a variety of known coronaviruses, appears safe in humans, and is capable of triggering broadly neutralizing antibodies or other relevant immune responses in people.

If a pancoronavirus vaccine gets authorized, would countries create stockpiles to quickly extinguish an outbreak of a new virus.

Efforts have already begun to develop second generation COVID-19 vaccines that could protect against those variants.