COVID-19 Innovations: Caltech’s Nanoparticle Technology Holds Promise for Protecting Against Many Coronavirus Strains at Once
: A new U.S.NIH-funded study led by researchers from Division of Biology and Biological Engineering, California Institute of Technology (Caltech) shows the potential of a remarkably adaptable, nanoparticle-based approach to coronavirus vaccine development.
A new coronavirus vaccine approach works by attaching many spike protein receptor-binding domains
(RBDs) to an engineered protein-based nanoparticle. In mice, the vaccine induced a cross-reactive
antibody response capable of neutralizing many different coronavirus strains.
Credit: Adapted from image by A. Cohen via BioRender
According to the researchers from the study abstract, “Protection against SARS-CoV-2 and SARS-related emergent zoonotic coronaviruses is urgently needed. We made homotypic nanoparticles displaying the receptor-binding domain (RBD) of SARS-CoV-2 or co-displaying SARS-CoV-2 RBD along with RBDs from animal betacoronaviruses that represent threats to humans (mosaic nanoparticles; 4-8 distinct RBDs). Mice immunized with RBD-nanoparticles, but not soluble antigen, elicited cross-reactive binding and neutralization responses. Mosaic-RBD-nanoparticles elicited antibodies with superior cross-reactive recognition of heterologous RBDs compared to sera from immunizations with homotypic SARS-CoV-2–RBD-nanoparticles or COVID-19 convalescent human plasmas. Moreover, sera from mosaic-RBD–immunized mice neutralized heterologous pseudotyped coronaviruses equivalently or better after priming than sera from homotypic SARS-CoV-2–RBD-nanoparticle immunizations, demonstrating no immunogenicity loss against particular RBDs resulting from co-display. A single immunization with mosaic-RBD-nanoparticles provides a potential strategy to simultaneously protect against SARS-CoV-2 and emerging zoonotic coronaviruses.”
The study findings were published in the peer reviewed journal: Science. https://science.sciencemag.org/content/early/2021/01/11/science.abf6840
The COVID-19 vaccines currently authorized for human use by the U.S. Food and Drug Administration (FDA) work by using mRNA to instruct our cells to make an essential portion of the spike protein of SARS-CoV-2, which is the novel coronavirus that causes COVID-19.
As our immune system learns to recognize this protein fragment as foreign, it produces antibodies to attack SARS-CoV-2 and prevent COVID-19. What makes the new vaccine technology so powerful is that it raises the possibility of training the immune system to recognize not just one strain of coronavirus but up to eight with a single shot.
To date this approach has not yet been tested in human, but when a research team, led by Dr Pamela Bjorkman from California Institute of Technology injected this new type of vaccine into mice, it spurred the production of antibodies that react to a variety of different coronaviruses.
Importantly some of the mouse antibodies proved to be reactive to related strains of coronavirus that weren’t even represented in the vaccine. These findings suggest that if presented with multiple different fragments of the spike protein’s receptor binding dom
ain (RBD), which is what SARS-like coronaviruses use to infect human cells, the immune system may learn to recognize common features that might protect against as-yet unknown, newly emerging coronaviruses.
This new innovative research and development utilizes a technology called a mosaic nanoparticle vaccine platform.
This innovation was originally developed by collaborators at the University of Oxford, United Kingdom, the nanoparticle component of the platform is a “cage” made up of 60 identical proteins. Each of those proteins has a small protein tag that functions much like a piece of Velcro®.
For this new technology, Dr Bjorkman and her colleagues, including graduate student Dr Alex A. Cohen, engineered multiple different fragments of the spike protein so each had its own Velcro-like tag. When mixed with the nanoparticle, the spike protein fragments stuck to the cage, resulting in a vaccine nanoparticle with spikes representing four to eight distinct coronavirus strains on its surface. In this instance, the researchers chose spike protein fragments from several different strains of SARS-CoV-2, as well as from other related bat coronaviruses thought to pose a threat to humans.
The study team then injected the vaccine nanoparticles into mice and the results were encouraging. After inoculation, the mice began producing antibodies that could neutralize many different strains of coronavirus.
Although more study is needed to understand the mechanisms, the antibodies responded to coronavirus strains that weren’t even represented on the mosaic nanoparticle.
Most importantly, this broad antibody response came without apparent loss in the antibodies’ ability to respond to any one particular coronavirus strain.
The study findings raise the exciting possibility that this new vaccine technology could provide protection against many coronavirus strains with a single shot. Of course, far more study is needed to explore how well such vaccines work to protect animals against infection, and whether they will prove to be safe and effective in people. There will also be significant challenges in scaling up manufacturing.
The goal is not to replace the mRNA COVID-19 vaccines that scientists developed at such a remarkable pace over the last year, but to provide much-needed vaccine strategies and tools to respond swiftly to the emerging coronavirus strains of the future.
Most importantly as researchers double down on efforts to combat COVID-19, they must also come to grips with the fact that SARS-CoV-2 isn’t the first and surely won’t be the last novel coronavirus to cause disease in humans. With continued research and development of new technologies such as this one, the hope is that they will come out of this terrible pandemic better prepared for future infectious disease threats or maybe not.
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