I have discussed in previous posts the role of antibodies in cancer treatment and how a variety of medical tests for different conditions rely on detection of antibodies we make in response to foreign threatening organisms that enter our bodies.
Immunologists are also looking into antibodies made by other animals for their potential use in humans to treat diseases, including COVID-19. Our antibodies are Y-shaped molecules containing different “domains” called heavy and light chains (two of each). Camelid antibodies from a family of animals including dromedary camels, llamas, and alpaca, are also shaped as a Y but contain only heavy chains, making them a bit smaller in size (see figure below). At the end of the two arms of these open Y antibodies there are “variable” domains that are responsible for recognizing (and binding to) different antigens in response to infections. Whereas the variable antigen-recognizing domain of human antibodies has two components (from a heavy and a light chain, respectively), the camelid antibodies have only one, from their heavy chains. This “single domain” that recognizes the antigen of choice has been named “nanobody”, with this type of antibodies produced and isolated in good amounts in approaches used as the source of antibody tools in biotechnology research as well as therapies for specific diseases. The drug caplacizumab was the first nanobody-derived therapy- approved in 2018, it is used in patients with “acquired thrombotic thrombocytopenic purpura” to prevent blood clotting.
Immunologists are also looking into antibodies made by other animals for their potential use in humans to treat diseases, including COVID-19. Our antibodies are Y-shaped molecules containing different “domains” called heavy and light chains (two of each). Camelid antibodies from a family of animals including dromedary camels, llamas, and alpaca, are also shaped as a Y but contain only heavy chains, making them a bit smaller in size (see figure below). At the end of the two arms of these open Y antibodies there are “variable” domains that are responsible for recognizing (and binding to) different antigens in response to infections. Whereas the variable antigen-recognizing domain of human antibodies has two components (from a heavy and a light chain, respectively), the camelid antibodies have only one, from their heavy chains. This “single domain” that recognizes the antigen of choice has been named “nanobody”, with this type of antibodies produced and isolated in good amounts in approaches used as the source of antibody tools in biotechnology research as well as therapies for specific diseases. The drug caplacizumab was the first nanobody-derived therapy- approved in 2018, it is used in patients with “acquired thrombotic thrombocytopenic purpura” to prevent blood clotting.
Figure modified from Figure 1 Resemann et al, 2010, J Biomol Tech 21(3 Suppl):S49.
The camelids can produce these nanobody-containing antibodies when immunized with specific antigens, such as the spike protein of the SARS-CoV-2 virus that causes COVID-19. Because of their tiny size, they don’t trigger an immune response in humans. These antibodies can be isolated from blood samples and analyzed in the lab for activity against SARS-CoV-2 in an infection assay using the virus and human cells in a cell-culture dish.
Nanobodies from llamas were tested in the lab for “neutralization” of the COVID-19 causing virus SARS-CoV-2, in other words whether they bind to the virus’ spike protein that binds to ACE2 receptors present in human cells in order to enter and invade these cells. The spike protein, critical for virus infection, is currently also the main target of COVID-19 vaccines approved and in development.
Nanobodies in general offer several advantages in diverse applications, all mainly derived from its small size compared with human antibodies (10 times smaller), including easier and more affordable manufacturing in large scale. They are also very stable at long-term, and could be delivered by an inhaler directly to the lungs, as opposed to traditional antibody therapies that are delivered intravenously, are much more expensive to produce and require much higher amounts to be delivered as an effective treatment. The possibility of using nebulization to deliver a nanobody treatment is very appealing in the case of respiratory infections such as COVID-19, as it allows nanobodies to reach the lungs quickly and directly to block viral invasion. Nanobodies can also be made in microbial cells (bacteria and yeast).
Nanobodies in general offer several advantages in diverse applications, all mainly derived from its small size compared with human antibodies (10 times smaller), including easier and more affordable manufacturing in large scale. They are also very stable at long-term, and could be delivered by an inhaler directly to the lungs, as opposed to traditional antibody therapies that are delivered intravenously, are much more expensive to produce and require much higher amounts to be delivered as an effective treatment. The possibility of using nebulization to deliver a nanobody treatment is very appealing in the case of respiratory infections such as COVID-19, as it allows nanobodies to reach the lungs quickly and directly to block viral invasion. Nanobodies can also be made in microbial cells (bacteria and yeast).
RSS Feed