New vaccine protects against COVID-19 and variants in pre-clinical studies
Posted: 11 May 2021 | Victoria Rees (Drug Target Review) | No comments yet
A new vaccine has shown promise at protecting monkeys and mice from COVID-19, its variants and other coronaviruses.
A potential new vaccine has proven effective in protecting monkeys and mice from a variety of coronavirus infections – including SARS-CoV-2 as well as the original SARS-CoV-1 and related bat coronaviruses that could potentially cause the next pandemic. The COVID-19 vaccine was created at Duke University, US.
The new vaccine triggers neutralising antibodies via a nanoparticle. The nanoparticle is composed of the receptor-binding domain (RBD), located on the Spike (S) protein, that links the viruses to receptors in human cells. While this binding site enables it to enter the body and cause infection, it can also be targeted by antibodies. The vaccine is also formulated with an adjuvant.
“We began this work last spring with the understanding that, like all viruses, mutations would occur in the SARS-CoV-2 virus, which causes COVID-19,” said senior author Dr Barton Haynes. “The mRNA vaccines were already under development, so we were looking for ways to sustain their efficacy once those variants appeared. This approach not only provided protection against SARS-CoV-2, but the antibodies induced by the vaccine also neutralised variants of concern that originated in the UK, South Africa and Brazil. And the induced antibodies reacted with quite a large panel of coronaviruses.”
The team built on earlier studies involving Severe Acute Respiratory Syndrome (SARS), caused by SARS-CoV-1. They found a person who had been infected with SARS developed antibodies capable of neutralising multiple coronaviruses, suggesting that a pan-coronavirus might be possible.
The researchers identified one particular RBD site that is present on SARS-CoV-2, its circulating variants and SARS-related bat viruses that makes them highly vulnerable to cross-neutralising antibodies.
The team then designed a nanoparticle displaying this vulnerable spot. The nanoparticle is combined with a small molecule adjuvant – specifically, the toll-like receptor 7 and 8 agonist called 3M-052, formulated with Alum, which was developed by 3M and the Infectious Disease Research Institute.
In tests of its effect on monkeys, the nanoparticle vaccine blocked COVID-19 infection by 100 percent. The new vaccine also elicited significantly higher neutralising levels in the animals than current vaccine platforms or natural infection in humans.
“Basically what we have done is take multiple copies of a small part of the coronavirus to make the body’s immune system respond to it in a heightened way,” said lead author Dr Kevin Saunders. “We found that not only did that increase the body’s ability to inhibit the virus from causing infection, but it also targets this cross-reactive site of vulnerability on the S protein more frequently. We think that is why this vaccine is effective against SARS-CoV-1, SARS-CoV-2 and at least four of its common variants, plus additional animal coronaviruses.”
“There have been three coronavirus epidemics in the past 20 years, so there is a need to develop effective vaccines that can target these pathogens prior to the next pandemic,” Haynes said. “This work represents a platform that could prevent, rapidly temper, or extinguish a pandemic.”
The findings appear in Nature.
Drug Development, Immunology, In Vivo, Vaccine
Covid-19, Severe Acute Respiratory Syndrome (SARS)
Dr Barton Haynes, Dr Kevin Saunders