“Nanobody” can hold clues to new COVID-19 therapy

WEHI researchers study “Nanobodies” (small immune proteins made by alpaca) to understand whether they are effective in blocking SARS-CoV-2, the virus that causes COVID-19. doing.

Alpaca creates something unique antibodyCalled Nanobodies, they can bind very specifically to proteins. The research team is developing Nanobodies specific for the SARS-CoV-2 “spike” protein. It sticks out of the surface of the virus and allows the virus to bind and invade human cells.

The team hopes that the development of nanobodies for “spiked” proteins will be an important step towards a new antibody-based “biological” therapy for the treatment of COVID-19.

This nanobody program for COVID-19 is part of a consortium-led effort to bring together the expertise of Victorian and Australian academic and industry leaders. Infection Antibody treatment at WEHI, Doherty Institute, CSL, Affinity Bio, CSIRO, Burnet Institute, Kirby Institute.

Nanobodies — components of antibody-based therapies

Antibodies are proteins that fight important infections in our immune system. An important aspect of an antibody is that it binds tightly and specifically to another protein, said Associate Professor Waihontam, who leads WEHI’s research.

“Antibody-based therapies, or” biologics, “take advantage of this property of antibodies to utilize antibodies that specifically bind to the proteins involved in the disease.In our case, we Treatment It binds to the SARS-CoV-2 virus “spike” protein and uses it to invade human cells. These antibodies may prevent the virus from binding to a human receptor called ACE2 and block the COVID-19 infection cycle. “

Alpaca habit Immune system create alpaca Antibodies are an important resource for this project.

“Alpaca creates unique antibodies that are smaller than traditional antibodies. Traditional antibodies are composed of two immunoglobulins, a heavy chain and a light chain, while alpaca is the majority of antibodies that lack a light chain. Nanobodies are heavy chain antibody fragments created in the laboratory. Chain-only domains that recognize foreign proteins. They bind very specifically to the target protein and are more stable than other antibodies. “We do,” said Tam.

To generate Nanobodies against SARS-CoV-2, a group of alpaca in Victoria has been immunized with synthetic non-infectious agents that are part of the SARS-CoV-2 “spiked” protein.

“Synthetic” spike “proteins are not infectious and do not cause alpaca to develop disease, but they can cause alpaca to develop Nanobodies,” said Tam.

“Then you can extract the gene sequences that encode Nanobodies and use them to generate millions of Nanobodies in the laboratory and select those that bind to the” spike “protein. “

“Currently, we are comparing these Nanobodies and discovering the ones that are most effective at binding to” spike “proteins and blocking the virus from entering cells. These antibodies have the potential to enable the development of new therapies for COVID-19. “

ANSTO’s Australian Synchrotron is an important resource of the project, allowing the research team to map which part of the “spike”. protein The bound Nanobodies and how they affected the virus’s ability to bind to human receptors.

Use of antibody therapy to treat COVID-19

Antibody therapy has already been done Clinical use For diseases such as cancer, inflammatory and autoimmune conditions.

They can be used for both prevention and treatment of illness and are especially useful for the elderly and immunocompromised people who may not be able to initiate a strong immune response to the vaccine.

Associate Professor Tam said antibody-based therapies are different from vaccines.

“Vaccines elicit an immune response to produce antibodies, but antibody-based therapies deliver effective antibodies directly, which means that antibody-based therapies begin to work immediately. However, it does not provide long-term protection. In contrast, vaccines take some time. It is time to build protective immunity, which can last months, years, or even decades. There is sex. “

The research is in its infancy, but the team hopes it will help fight COVID-19.

“We are in the early stages of this study and there are many steps that need to be taken in treatment development and clinical trials before using this treatment in humans, but we hope for antibodies. It’s a base treatment. It offers one potential solution to COVID-19 and can be used in conjunction with other treatments to combat this global pandemic, “said Associate Professor Tam. I did.

“We do not yet know when these treatments for COVID-19 will be generally available, but we will do our best to make them available as quickly and safely as possible. Scientifically mobilize in such areas. I’ve never seen a group of people who are. It’s a passionate and collaborative way. ”