The normal antibody (immunoglobulin) has two light chains and two heavy chains. Each chain, be it light or heavy, has a variable and a constant fragment. The variable fragment binds to the putative antigen, while the constant fragment carries the Fc receptor that lets cells like NK cells and neutrophils bind to the antibody. The constant portion also binds and activates complement through the classical pathway.
in 1984, Raymond Hamers at the VUB university in Brussels, while analysing the blood of dromedary camels for antibody response to a Trypanosomal species (the dromedary camel is the Arabian camel, with a single hump, as opposed to the double humped Bactrian camel, found in the plains of Central Asia), found to his surprise that the camel antibodies did not look like the human counterparts at all. They lacked the light chain altogether, and contained only the heavy chain, comprised of the variable and heavy fragments. Quite appropriately, these antibodies were named "camelids".
The 1990s saw the establishment of phage display libraries, which allow the manufacture of virtually any antibody in bacteria, by inserting the relevant sequence in bacteriophages, which then infect the bacteria, and uses the bacterial enzymes to make the protein whose sequence has been inserted into the phage. This technique is responsible for producing most monoclonal antibodies these days, having moved on from the days when antibody producing B-cells were immortalised by fusing them with rat myeloma plasmablasts, a technique described as hybridoma.
It is now possible to produce through such phage display techniques, not just whole immunoglobulin molecules, but parts thereof, such as a the Fab fragment (commercially marketed as Certolizumab), a single chain variable fragment, the camelid (commercial application Caplacizumab, used to treat acquired thrombotic thromobocytopenic purpura), or an isolated variable heavy chain fragment, called VHH. Please see Diagram.
It is the VHH, or the variable heavy chain single domain antibody that now provides promise for the treatment of COVID-19. While vaccines can take years, and canonical (standard) monoclonal antibodies around 6 months to prepare, VHH can be prepared very quickly- within weeks, and therefore are ideally suited for dealing with a pandemic. Please see the linked paper in Cell below:
https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30250-X
VHH has several advantages over other techniques. It ways around 15 kDa, around a tenth of the full immunoglobulin molecule. It can reach antigenic epitopes that the full immunoglobulin molecule cannot reach, such as hidden epitopes, a fact that is relevant with COVID-19. And it does not have the foreign antigenicity that full camelids have, thus reducing the risk that they would be rendered ineffective by the human immune system.
in 1984, Raymond Hamers at the VUB university in Brussels, while analysing the blood of dromedary camels for antibody response to a Trypanosomal species (the dromedary camel is the Arabian camel, with a single hump, as opposed to the double humped Bactrian camel, found in the plains of Central Asia), found to his surprise that the camel antibodies did not look like the human counterparts at all. They lacked the light chain altogether, and contained only the heavy chain, comprised of the variable and heavy fragments. Quite appropriately, these antibodies were named "camelids".
The 1990s saw the establishment of phage display libraries, which allow the manufacture of virtually any antibody in bacteria, by inserting the relevant sequence in bacteriophages, which then infect the bacteria, and uses the bacterial enzymes to make the protein whose sequence has been inserted into the phage. This technique is responsible for producing most monoclonal antibodies these days, having moved on from the days when antibody producing B-cells were immortalised by fusing them with rat myeloma plasmablasts, a technique described as hybridoma.
It is now possible to produce through such phage display techniques, not just whole immunoglobulin molecules, but parts thereof, such as a the Fab fragment (commercially marketed as Certolizumab), a single chain variable fragment, the camelid (commercial application Caplacizumab, used to treat acquired thrombotic thromobocytopenic purpura), or an isolated variable heavy chain fragment, called VHH. Please see Diagram.
It is the VHH, or the variable heavy chain single domain antibody that now provides promise for the treatment of COVID-19. While vaccines can take years, and canonical (standard) monoclonal antibodies around 6 months to prepare, VHH can be prepared very quickly- within weeks, and therefore are ideally suited for dealing with a pandemic. Please see the linked paper in Cell below:
https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(20)30250-X
VHH has several advantages over other techniques. It ways around 15 kDa, around a tenth of the full immunoglobulin molecule. It can reach antigenic epitopes that the full immunoglobulin molecule cannot reach, such as hidden epitopes, a fact that is relevant with COVID-19. And it does not have the foreign antigenicity that full camelids have, thus reducing the risk that they would be rendered ineffective by the human immune system.
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