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Nanoparticle Technology Holds Promise for Protecting Against Many Coronavirus Strains at Once

Posted on by Dr. Francis Collins

Mosaic vaccine
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

It’s truly encouraging to witness people all across our nation rolling up their sleeves to get their COVID-19 vaccines. That is our best chance to end this pandemic. But this is the third coronavirus to emerge and cause serious human illness in the last 20 years, and it’s probably not the last. So, this is also an opportunity to step up our efforts to develop vaccines to combat future strains of disease-causing coronavirus. With this in mind, I’m heartened by a new NIH-funded study showing the potential of a remarkably adaptable, nanoparticle-based approach to coronavirus vaccine development [1].

Both COVID-19 vaccines currently authorized for human use by the 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.

This approach has not yet been tested in people, but when a research team, led by Pamela Bjorkman, California Institute of Technology, Pasadena, injected this new type of vaccine into mice, it spurred the production of antibodies that react to a variety of different coronaviruses. In fact, 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 domain (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 work, published in the journal Science, utilizes a technology called a mosaic nanoparticle vaccine platform [1]. 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®. In their SARS-CoV-2 work, Bjorkman and her colleagues, including graduate student 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 researchers 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. In fact, while more study is needed to understand the mechanisms, the antibodies responded to coronavirus strains that weren’t even represented on the mosaic nanoparticle. Importantly, this broad antibody response came without apparent loss in the antibodies’ ability to respond to any one particular coronavirus strain.

The 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. Our 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.

As we double down on efforts to combat COVID-19, we 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 we will come out of this terrible pandemic better prepared for future infectious disease threats.


[1] Mosaic RBD nanoparticles elicit neutralizing antibodies against SARS-CoV-2 and zoonotic coronaviruses. Cohen AA, Gnanapragasam PNP, Lee YE, Hoffman PR, Ou S, Kakutani LM, Keeffe JR, Barnes CO, Nussenzweig MC, Bjorkman PJ. Science. 2021 Jan 12.


COVID-19 Research (NIH)

Bjorkman Lab (California Institute of Technology, Pasadena)

NIH Support: National Institute of Allergy and Infectious Diseases


  • Steve White says:

    I am very alarmed by reports of the variant which is probably causing the renewed epidemic in Manaus being found in Minneapolis.
    I believe the procedures used at our borders to keep the variants out have been, and still are, completely inadequate.
    Media reports are, a traveler must test negative in the country of departure, then is allowed to fly, and, on arrival here, is told to quarantine for 7 days.
    This is surely not good enough. Obviously, the traveler can be infected in the airport, AFTER getting a negative test – and the quarantine here appears to be voluntary, not enforced by direct control. I have been told, in Taiwan, arriving travelers are put under guard (in hotels, not jails) by police.
    Perhaps worse of all, according to the media reports, these inadequate measures apply only to non-citizens. I understand there might be some legal reasons orders effecting US Citizens might not be made, but these need to be overcome.
    We may get lucky and stop this variant from spreading from Minneapolis – frankly it does not look good considering it has been almost a month since they arrived – but still with “Patient Zero” identified, maybe we can stop it.
    But we need to have real procedures in place to keep the variants out as long as possible …

  • Tina says:

    Does this covid shot cause infertility?

  • Merrit says:

    My thought is that this technology adds a micro-particle that is not part of the original mRNA vaccine to capture the various mRNA particles. This micro-particle was not part of the original vaccine concept and obviously will be injected so it is another foreign body that could result in an additional response by the immune system that is not useful and could be undesirable. The alternative is to just mix all of the various mRNA variants into the solution without the micro-particle holding them together. I guess that the difference is that with the micro-particle you can but sure that it is the same distribution of the various variants and with normal mixing it would not be as exact but there are many other pharma components that are just mixed together so I don’t understand why this is necessary. It seems like a technology that is looking for problem rather than a problem looking for a technology to solve it.

  • Kathryn Sargent says:

    Thanks for posting this, Francis! My youngest daughter and I were just discussing this last night! I’m sharing this with her!

  • Jim B says:

    Unlike simply mixing vaccine components in solution such as RNA or DNA based vaccines, this seems like it could really challenge the regulatory system since the product will be highly heterogenous due to symmetry (60 different proteins, and even if its simplified and comprised of only 2 or 3 spikes held together covalently on a nanoparticle, it will result in an incredibly (an materially uncharacterize-ably) high order mixture – like a giant box of 4x4x4 rubik cubes each randomly rotated. You could approve the process but biological lot to lot variation would be major issue.


    Could this technique also be used to develop more effective influenza vaccines?

  • top4d says:

    Nice blog, Very interesting!!

  • Jack schwartz says:

    Does the S1 protein produced by MRNA of the COVID vaccines cross the blood brain barrier to cause head ache etc issues similar to the virus infection itself?

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