As the world grapples with the challenges posed by the COVID-19 pandemic, researchers at the Duke Human Vaccine Institute (DHVI) have been working round the clock in pursuit of the holy grail of vaccines: one that protects against all kinds of coronaviruses. In other words, a vaccine that can stop future pandemics in its tracks. And now, the DHVI team is on the cusp of delivering just that.

“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,” said Professor Barton Haynes, Director of the DHVI. “This work represents a platform that could prevent, rapidly temper or extinguish a pandemic.”

A pan-coronavirus vaccine that could protect people against new variants as well as other coronaviruses has been considered for years, but the current pandemic brought it to the forefront of many researchers’ minds. Wanting to sustain the efficacy of the first mRNA vaccines against possible SARS-CoV-2 variants, DVHI set to work on a pan-coronavirus vaccine last year

Haynes, who is the senior author on this project, and lead author Associate Professor Kevin Saunders, Director of Research at DHVI, built on earlier work during which they found that a patient who had been infected with SARS developed antibodies capable of neutralising not just SARS-CoV-1 but also multiple coronaviruses.

Coronaviruses have receptor-binding domains, located on the spike that links the viruses to receptors in human cells. While binding sites enable the virus to enter the body and cause infection, they also serve as the virus’ Achilles heel as they can be targeted by antibodies.

Barton Haynes (left) and Kevin Saunders (right)
 

The research team identified one particular receptor-binding domain site that was present on SARS-CoV-2, its circulating variants and other SARS-related bat viruses, making them highly vulnerable to cross-neutralising antibodies.

The team then designed a nanoparticle displaying multiple copies of this vulnerable spot, with the aim of triggering neutralising antibodies in patients. The nanoparticle was combined with a small molecule adjuvant—specifically, the toll-like receptor 7 and 8 agonist called 3M-052. Testing of the nanoparticle vaccine candidate soon began, with promising results obtained. The findings were published in Nature in May.

“What we’ve 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,” Saunders said. “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 spike protein more frequently.”

“This approach not only provided protection against SARS-CoV-2 but the antibodies induced by the vaccine also neutralised variants of concern,” said Haynes. “And the induced antibodies reacted with quite a large panel of coronaviruses.”

Though the vaccine has yet to progress to first-in-man studies, it was singled out by Dr Anthony Fauci, Director of the National Institutes of Allergy and Infectious Disease and White House Senior Advisor on the pandemic, during a White House briefing in March.

“In monkeys, the nanoparticle vaccine completely blocked SARS-CoV-2 infection and elicited higher neutralising antibody activity than seen with current vaccines or with natural infection,” said Fauci.

While the data will require further validation, Fauci is optimistic about DHVI’s efforts: “This is an extremely important proof of concept that we will be aggressively pursuing as we get into the development of human trials.”
 

Edited by Chua Li Min and Drima Chakraborty. Adapted from: Duke TODAY and Duke Health