Small biotech launches human trials of a potential ‘backstop’ for Covid-19 vaccines

A small biotechnology firm said that it will start human testing of an experimental Covid-19 vaccine it hopes can target potential strains of the SARS-CoV-2 virus that could evade current vaccines — if such strains ever exist and become a problem.

“We all hope that this will not be necessary,” said Andrew Allen, the CEO of the firm, Gritstone Oncology, in an interview with STAT. “I think it’s prudent to have it developed as a backstop. We all talk about pandemic preparedness. So that’s what this is about.”

“We have a good vaccine that is delivering benefit in the short term, but we need to be ready for scenarios where those vaccines lose effectiveness, because that historically has been seen many times and we should be ready for that and not be caught short again,” Allen said.

It’s not clear whether such a shot will be needed. But the effort, though a long-shot, is evidence of the deep well of pharmaceutical research backing up the vaccine effort.

Preclinical work on the vaccine has been supported by the Bill and Melinda Gates Foundation. A phase 1 clinical trial will be conducted by the National Institute for Allergy and Infectious Disease, with Gritstone paying for the production of the vaccine candidate. There is no publicly available data on the preclinical research.

Gritstone is hardly a major player. The company went public in Sept. 2018, raising $100 million. Shares traded as high as $28 before falling to their current $6.39 as investors became less enthused with the prospects for the firm’s strategy of using vaccine technology to develop cancer immunotherapies. It currently has a market capitalization of just $300 million.

The company’s effort joins an already robust spread of Covid-19 vaccine research. The World Health Organization counts 64 such projects in development. Two vaccines, one from Pfizer and partner BioNTech and another from Moderna, have been cleared for emergency use in the U.S. so far.

But Allen said that the emergence of a new strain in South Africa helped convince the company that it was important to develop its own version. In lab experiments, one of the mutations present in the variant identified in South Africa and seen separately in another variant found later Brazil — called E484K — helped the virus dodge the protective antibodies that are sometimes generated after an initial infection.

This week, scientists in South Africa reported that antibodies from some of those previously infected failed to recognize the newer variant. There still aren’t results about how the variant interacts with antibodies produced after vaccination.

Allen noted that current vaccines are all targeted against what is known as the spike protein, a tool SAR-CoV-2 uses to grapple its way into cells. Gritstone would aim for its vaccine to create an innate immune response to other antigens in the virus, making it even harder for the virus to evade.

The Gritstone approach combines two different types of vaccines. The first dose would be a vaccine based on adenovirus, a group of viruses that can cause cold-like illnesses. This is similar to the vaccines being developed by Johnson and Johnson and, separately, by the team of Oxford University and AstraZeneca. The virus is used to introduce a gene into cells, which then produce proteins to which the immune system mounts a response. But the second dose would be an mRNA vaccine, much like the vaccines developed by Moderna and the team of Pfizer and BioNTech.

A brand new vaccine is not the only way to combat a new variant. An alternative strategy would be to rapidly produce new versions of the existing vaccines, such as those from Moderna or t Pfizer/BioNTech, to combat a new strain.

One difficulty of developing any new vaccine will be testing it. The first crop of Covid-19 vaccines were tested against placebo in giant clinical trials of 30,000 volunteers or more. But over the coming year, most people will be vaccinated. And with a vaccine available, it may no longer be ethical to conduct placebo-controlled studies.

Researchers have not yet settled on how to use other criteria, like antibody response created by a vaccine or the activity of immune cells called T-cells, to predict if a vaccine will work.

Daniel Hoft, director of Saint Louis University’s Center for Vaccine Development and lead principal investigator of Gritstone’s COVID study, said large clinical trials could be necessary, potentially testing the vaccine against one of the approved vaccines to see if the new vaccine was roughly equivalent, or non-inferior. That could be a long path.