The underdog coronavirus vaccines that the world will need if front runners stumble

When it comes to developing vaccines, Peter Palese is no slouch. A virologist at Icahn School of Medicine at Mount Sinai in New York City, he pioneered genetics techniques that are used to make some of the billions of influenza vaccine doses produced annually, and his team has won millions of dollars to develop a universal flu jab.

Palese is developing a COVID-19 vaccine, too. It consists of a bird virus genetically modified to make a protein found on the surface of the SARS-CoV-2 coronavirus. The vaccine fully protects mice from an experimental model of COVID-191, according to a recent preprint (the research has not yet been peer reviewed). It also grows in chicken eggs, like most flu vaccines, so manufacturing could be ramped up using tried-and-tested technology.

Despite its potential, Palese’s vaccine has struggled to gain the attention and funding needed to progress to human trials. “We thought this would be the best thing after sliced bread, and people would break down our doors to get it. That’s not the case. We are very disappointed,” he says.As leading pharmaceutical and biotechnology companies speed their COVID-19 vaccines through clinical trials and eye up fast-track regulatory authorization, dozens of underdog vaccines such as Palese’s have stalled, or are advancing along a slower, more conventional path.

Scientists acknowledge that it would be a waste of resources to take every candidate to clinical trials. But they argue that it’s essential to have a diverse selection of COVID-19 vaccines in development. Early favourites could fail, confer only partial protection or work poorly in certain age groups; high costs and other barriers might make some of the front runners unsuitable for wide-scale deployment in lower-income countries.

“Everyone is rooting for them to succeed beyond anyone’s expectation, but it’s prudent to think about what happens if they don’t,” says Dave O’Connor, a virologist at the University of Wisconsin–Madison. “We need to make sure we have back-up plans — and back-up plans to those back-up plans.”There are more than 320 COVID-19 vaccines in development, according to a recent tally by the Coalition for Epidemic Preparedness Innovation (CEPI) in Oslo, a fund created to finance and coordinate vaccines for outbreaks. Most of these are in the early stages of preclinical development; several dozen are in clinical trials, and only a handful have begun final-phase tests for efficacy. “Everybody and their mother has a vaccine. My dogs have two vaccines,” says one scientist working on a leading candidate. Although on the face of it this is good news, it also presents challenges. One is determining which candidates should move forward to costly clinical trials: running even a small study to test safety and dosing is beyond the reach of most academic groups, and smaller teams face an uphill struggle to get their candidates noticed.

In some cases, the breakneck pace of COVID-19 vaccine efforts has created openings for academic groups. One of the leading candidates is being developed by the University of Oxford, UK, and drug company AstraZeneca (trial enrolment was paused after a participant developed a serious health problem, the company said on 8 September). The vaccine is based on a kind of chimpanzee cold virus, called an adenovirus, that has been used for experimental vaccines against Ebola, malaria and other diseases, allowing Oxford vaccinologists to quickly adapt the platform to a COVID-19 vaccine. Another technology comprises RNA instructions for a coronavirus protein, and two front-runner vaccines are being developed by firms with expertise in that platform.