Cuerpos nanos podrían tener pistas de nuevas terapias para Covid-19
Las alpacas producen anticuerpos únicos - llamados cuerpos nanos - que pueden ligarse específicamente a una proteína. El equipo de investigación está desarrollando cuerpos nanos específicos para la proteína 'pico' específica del SARS-CoV-2, la que surge de la superficie del virus y le permite ligarse y penetrar en células humanas.
El equipo espera que el hecho de desarrollar cuerpos nanos contra esta proteína 'pico' podría ser un paso importante hacie nuevas terapias basadas en anticuerpos para tratar la COVID-19.
Este programa de cuerpos nano contra la COVID-19 es una parte de un esfuerzo conducido por un consorcio que une el conocimiento de experto de líderes académicos e industriales victorianos y australianos en enfermedades infeccionas y terapéuticas de anticuerpos en WEHI, el Instituto Doherty, CSL, Affinity Bio, CSIRO, el Instituto Burnet y el Instituto Kirby.
Cuerpos nano - los bloques de construcción de terapias basadas en anticuerpos
Los anticuerpos son proteínas de lucha claves en nuestro sistema de inmunidad. Un aspecto importante de los anticuerpos es que ellos se ligan ajustadamente y específicamente a otra proteína, dice el profesor asociado Wai-Hong Tham, que está a cargo de la investigación en el WEHI.
"Terapias basadas en anticuerpos o 'biológicas' utilizan esta propiedad de los anticuerpos, aprovechando un anticuerpo que se liga específicamente a una proteína involucrada en una enfermedad. En nuestro caso, estamos recurriendo a desarrollar una terapia que se ligue a la proteína 'pico' del virus SARS-CoV-2, la que éste usa para penetrar en células humanas. Estos anticuerpos podrían evitar que el virus se ligue al receptor humano llamado ACE - interrumpiendo el ciclo de infección de la COVID-19, dice ella.
Una peculiaridad del sistema de inmunidad de las alpacas puede convertir los anticuerpos de alpaca en un recurso clave en este proyecto.
"Las alpacas hacen anticuerpos únicos, los que son más pequeños que los anticuerpos convencionales. Los anticuerpos convencionales están compuestos de dos inmunoglibinas - cadenas pesadas y cadenas livianas - mientras que las alpacas hacen la mayoría de los anticuerpos que carecen de las cadenas livianas. Los cuerpos nano son fragmentos de anticuerpos hechos en laboratorio los únicos dominios de la cadena pesada que reconocen proteínas extrañas. éstas se ligan realmente específicamente a su proteína de meta y son más estables que otros anticuerpos.", dijo la profesora Tham.
Para generar anticuerpos contra el SARS-CoV-2, un grupo de alpacas en la regional Victoria están siendo inmunizadas con una parte sintética, no infecciosa de la proteína pico del SARS-CoV-2.
"La proteína 'pico' sintética no es infecciosa y no causa que las alpacas contraigan la enfermedad - pero ella permite que las alpacas desarrollen anticuerpos," dijo la profesora Tham.
"Podemos entonces extraer las secuencias de gen que codifican los anticuerpos y usar estas para producier millones de tipos de anticuerpos en laboratorio y entonces seleccionar los que se ligan a la proteína 'pico'.
"Estamos comparando ahora estos anticuerpos para descubrir cuales son los más efectivos en ligarse a la proteína 'pico' y bloquear el virus de entrar a las células. Estos anticuerpos podría permitir el desarrollo de nuevos tratamientos contra la COVID-19."
El Synchrotron australiano de ANSTO fue un recursop crítico en este proyecto, permitiendo al equipo de investigación representar cuales partes de la proteína 'pico' a las que se ligan los anticuerpos y como ésto impactó la capacidad del virus de ligarse a su receptor humano.
Usando terapias de anticuerpos para tratar la COVID-19
Las terapias de anticuerpos ya son utilizadas en uso clínico para enfermedades como el cáncer, inflamatorias y autoinmunes.
Ellas pueden ser utilizadas tanto para impedir como tratar enfermedades y son particularmente útiles en personas ancianas o en aquellos que tienen problemas de inmunidad, quienes podrían no ser capaces de montar una respuesta inmune robusta a una vacuna.
La profesora Tham dijo que las terapias basadas en anticuerpos diferían de las vacunas.
"Las vacunas obtienen una respuesta inmune para producir anticuerpos, mientras que las terapias basadas en anticuerpos entregan los anticuerpos efectivos directamente. Mientras que ésto significa que las terapias basadas en anticuerpos comienzan a trabajar inmediatamente, podrían no proporcionar una protección a largo plazo. En contraste, una vacuna toma algún tiempo para construir una inmunidad protectora, pero esta inmunidad puede durar meses, años, o décadas."
La investigación está en un estado temprano, pero el equipo está esperanzado de que va a ayudar en la lucha contra la COVID-19.
"Estamos en las etapas tempranas de esta investigación y hay una cantidad de pasos que necesitamos tomar en su desarrollo, tanto como ensayos clínicos, antes de que este tratamiento pueda ser útil en seres humanos. Pero estamos esperanzados en que las terapias basadas en anticuerpos puedan ofrecer una solución en potencia a la COVID-19 y puedan ser usadas paralelamente con otros métodos de tratamiento para combatir esta pandemia global," dijo la profesora Tham.
"Mientras que no estamos seguros aún cuando estos tratamiento para la COVID-19 van a ser accesibles al público, estamos trabajando todo lo duramente que podemos para hacer a éstos accesibles con seguridad tan pronto como sea posible. Yo no he visto nunca equipos de personas mobilizándose científicamente de tal manera apasionada y colaborativa."
Los investigadores de WEHI están estudiando 'cuerpos nanos' - minúsculas proteínas inmunológicas hechas por las alpacas - en una apuesta por comprender si pueden ser efectivas en bloquear el SARS-CoV-2, el virus que causa la COVID-19.
Extraído de https://nano-magazine.com/
Traducción de Ricardo Ferré
Nanobodies could hold clues to new Covid-19 therapies
Traducción de Ricardo Ferré
Nanobodies could hold clues to new Covid-19 therapies
Alpacas produce unique antibodies—called nanobodies—that can bind very specifically to a protein. The research team are developing nanobodies specific for the SARS-CoV-2 'spike' protein, which sticks out from the surface of the virus and allows the virus to bind and enter human cells.
The team hopes that developing nanobodies against the 'spike' protein could be an important step towards new antibody-based 'biologics' therapies to treat COVID-19.
This nanobody program against COVID-19 is part of a consortium-led effort that brings together the expertise of Victorian and Australian academic and industry leaders in infectious diseases and antibody therapeutics at WEHI, the Doherty Institute, CSL, Affinity Bio, CSIRO, the Burnet Institute and the Kirby Institute.
Nanobodies—the building blocks for antibody-based therapies
Antibodies are key infection-fighting proteins in our immune system. An important aspect of antibodies is that they bind tightly and specifically to another protein, said Associate Professor Wai-Hong Tham, who is leading the research at WEHI.
"Antibody-based therapies—or 'biologics'—utilize this property of antibodies, harnessing an antibody that binds specifically to a protein involved in disease. In our case, we are looking to develop a therapy that binds to the SARS-CoV-2 virus' 'spike' protein, which it uses to get into human cells. These antibodies could prevent the virus binding to the human receptor called ACE2—stopping the COVID-19 infection cycle," she said.
A quirk of the alpaca immune system makes alpaca antibodies a key resource in this project.
"Alpacas make unique antibodies, which are smaller than conventional antibodies. Conventional antibodies are composed of two immunoglobin—heavy chains and light chains—whereas alpacas make the majority of antibodies that lack the light chains. Nanobodies are laboratory-made antibody fragments of the heavy chain only domain that recognizes foreign proteins. These bind really specifically to their target protein and are more stable than other antibodies," Associate Professor Tham said.
To generate nanobodies against SARS-CoV-2, a group of alpacas in regional Victoria are being immunized with a synthetic, non-infectious, part of the SARS-CoV-2 'spike' protein.
"The synthetic 'spike' protein is not infectious and does not cause the alpacas to develop disease—but it allows the alpacas to develop nanobodies," Associate Professor Tham said.
"We can then extract the gene sequences encoding the nanobodies and use this to produce millions of types of nanobodies in the laboratory and then select the ones that bind to the 'spike' protein."
"We are now comparing these nanobodies to discover which are the most effective at binding the 'spike' protein and blocking the virus from entering cells. These antibodies could enable the development of new treatments against COVID-19."
ANSTO's Australian Synchrotron was a critical resource in the project, allowing the research team to map which parts of the 'spike' protein the nanobodies bound to and how this impacted the virus' ability to bind to its human receptor.
Using antibody therapies to treat COVID-19
Antibody therapies are already in clinical use for diseases such as cancer, inflammatory and autoimmune conditions.
They can be used both to prevent and treat disease and are particularly useful in older people or those who are immunocompromised, who may not be able to mount a robust immune response to a vaccine.
Associate Professor Tham said antibody-based therapies differed from vaccines.
"Vaccines elicit an immune response to produce antibodies, whereas antibody-based therapies deliver the effective antibodies directly. While this means the antibody-based therapies start working straight away, they would not provide long-term protection. In contrast, a vaccine takes some time to build protective immunity, but this immunity can last for months, years or decades."
The research is at an early stage, but the team are hopeful it will help in the fight against COVID-19.
"We are in the early stages of this research and there are a number of steps that need to take place in developing the therapies, as well as clinical trials, before this treatment could be used in humans. But we are hopeful antibody-based therapies could offer one potential solution to COVID-19 and could be used alongside other treatment methods to combat this global pandemic," Associate Professor Tham said.
"While we are not sure yet when these treatments for COVID-19 will be available to the public, we are working as hard as we can to make these safely available as soon as possible. I have never seen groups of people mobilizing scientifically in such a passionate and collaborative way."
The team hopes that developing nanobodies against the 'spike' protein could be an important step towards new antibody-based 'biologics' therapies to treat COVID-19.
This nanobody program against COVID-19 is part of a consortium-led effort that brings together the expertise of Victorian and Australian academic and industry leaders in infectious diseases and antibody therapeutics at WEHI, the Doherty Institute, CSL, Affinity Bio, CSIRO, the Burnet Institute and the Kirby Institute.
Nanobodies—the building blocks for antibody-based therapies
Antibodies are key infection-fighting proteins in our immune system. An important aspect of antibodies is that they bind tightly and specifically to another protein, said Associate Professor Wai-Hong Tham, who is leading the research at WEHI.
"Antibody-based therapies—or 'biologics'—utilize this property of antibodies, harnessing an antibody that binds specifically to a protein involved in disease. In our case, we are looking to develop a therapy that binds to the SARS-CoV-2 virus' 'spike' protein, which it uses to get into human cells. These antibodies could prevent the virus binding to the human receptor called ACE2—stopping the COVID-19 infection cycle," she said.
A quirk of the alpaca immune system makes alpaca antibodies a key resource in this project.
"Alpacas make unique antibodies, which are smaller than conventional antibodies. Conventional antibodies are composed of two immunoglobin—heavy chains and light chains—whereas alpacas make the majority of antibodies that lack the light chains. Nanobodies are laboratory-made antibody fragments of the heavy chain only domain that recognizes foreign proteins. These bind really specifically to their target protein and are more stable than other antibodies," Associate Professor Tham said.
To generate nanobodies against SARS-CoV-2, a group of alpacas in regional Victoria are being immunized with a synthetic, non-infectious, part of the SARS-CoV-2 'spike' protein.
"The synthetic 'spike' protein is not infectious and does not cause the alpacas to develop disease—but it allows the alpacas to develop nanobodies," Associate Professor Tham said.
"We can then extract the gene sequences encoding the nanobodies and use this to produce millions of types of nanobodies in the laboratory and then select the ones that bind to the 'spike' protein."
"We are now comparing these nanobodies to discover which are the most effective at binding the 'spike' protein and blocking the virus from entering cells. These antibodies could enable the development of new treatments against COVID-19."
ANSTO's Australian Synchrotron was a critical resource in the project, allowing the research team to map which parts of the 'spike' protein the nanobodies bound to and how this impacted the virus' ability to bind to its human receptor.
Using antibody therapies to treat COVID-19
Antibody therapies are already in clinical use for diseases such as cancer, inflammatory and autoimmune conditions.
They can be used both to prevent and treat disease and are particularly useful in older people or those who are immunocompromised, who may not be able to mount a robust immune response to a vaccine.
Associate Professor Tham said antibody-based therapies differed from vaccines.
"Vaccines elicit an immune response to produce antibodies, whereas antibody-based therapies deliver the effective antibodies directly. While this means the antibody-based therapies start working straight away, they would not provide long-term protection. In contrast, a vaccine takes some time to build protective immunity, but this immunity can last for months, years or decades."
The research is at an early stage, but the team are hopeful it will help in the fight against COVID-19.
"We are in the early stages of this research and there are a number of steps that need to take place in developing the therapies, as well as clinical trials, before this treatment could be used in humans. But we are hopeful antibody-based therapies could offer one potential solution to COVID-19 and could be used alongside other treatment methods to combat this global pandemic," Associate Professor Tham said.
"While we are not sure yet when these treatments for COVID-19 will be available to the public, we are working as hard as we can to make these safely available as soon as possible. I have never seen groups of people mobilizing scientifically in such a passionate and collaborative way."
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