Developing new strategies and vaccine technologies is critical for controlling the pandemic and preparing for future outbreaks as the coronavirus continues to evolve and mutate, say the researchers.

The new method, described in the journal PLOS ONE, is an entirely unique approach to vaccination. Red blood-cell membranes are embedded with SARS-CoV-2 spike proteins, which then form virus-like particles.

“We take red blood cells and remove everything from the inside. We then attach spike proteins to their outside to mimic a corona virus,” explains graduate student Isabella Passos-Gastaldo, a lead author on the paper.

The particles, shown to activate the immune system and produce antibodies in mice, are completely harmless.

“Current vaccine delivery methods often cause drastic immune system reactions and have short-lived responses,” says Maikel Rheinstadter, a senior supervisor on the paper and a professor in the Department of Physics & Astronomy at McMaster.

“Some of the vaccines that have been developed have shown side effects. This delivery platform opens new possibilities for vaccines and therapeutics,” he says.

The researchers found cells can be loaded with a large dose of viral proteins, yet likely produce few side effects, making the new method more tolerable and effective than other vaccine options.

“We have developed a method where we can trigger an immune response without the use of genetic material and yet we are able to synthesize these particles in a very short amount of time,” says Sebastian Himbert, lead author on the study and a recent graduate student in the Department of Physics & Astronomy at McMaster.

The technology can be quickly adapted to develop vaccines for variants or new viruses that may emerge in future.

“This is the kind of creative, interdisciplinary research that McMaster is known for. It was exhilarating working with physicists, structural biologists and immunologists to design a radically different vaccine platform,” says Dawn Bowdish, Professor of Medicine at McMaster and Canada Research Chair in Aging & Immunity and co-author of the paper.

The researchers first reported this technique in 2020, when they modified red blood cells to deliver drugs throughout the body, which could then target infections or treat catastrophic diseases such as cancer or Alzheimer’s.

“This platform makes our own blood cells smart in many different ways,” explains Rheinstadter. “In this case it’s a vaccine. We are using our own cells much like nano robots inside of our bodies and whenever they see a disease, they can fight it.”

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In a study published this month in Science Advances, a team led by the University of Tsukuba found that D-serine serves as a chemical signal that allows tissue migration in marine sea squirts when they lose their tails on transforming from tadpoles into their mature form. Their findings offer a broader understanding of the chemical signals that occur during the organism’s transformation.

In mammals, D-serine binds to an ion channel found in neurons called the N-methyl-D-aspartate type glutamate receptor (NMDAR) to regulate the transmission of messages in the brain. D-serine also plays a functional role in mammalian skin tissue. However, its role in non-mammals is less understood, something the researchers at the University of Tsukuba aimed to address.

“D-serine has been detected in organisms such as insects, nematodes, and molluscs,” says lead author of the study, Professor Yasunori Sasakura. “Its global presence in metazoans is reflective of the conserved presence of a protein that converts L-serine to its D-form, called a serine racemase.”

The team’s previous results implicated a serine racemase in the tail regression of tadpoles of the marine sea squirt Ciona. In this study, they sought to clarify the role of D-serine in this process and found that D-serine is responsible for forming a pocket in the Ciona epidermis that allows the tail to regress into the main body. This pocket was formed by D-serine binding to NMDAR in the epidermis, causing the release of fluid-filled vesicles.

“The results were striking,” explains Professor Sasakura. “We found that the epidermal vesicle release in Ciona is quite similar to a process occurring in mammalian skin, involving a flux of cations mediated through NMDARs.”

To evaluate what happened when D-serine was absent during Ciona tail regression, the research team created a mutation that omitted the protein responsible for making D-serine from L-serine. Ciona organisms lacking this protein failed to complete tail regression, whereas regular Ciona organisms were able to successfully complete the process.

“Our findings provide insight into how epidermal homeostasis is maintained in animals, contributing toward further evolutionary perspectives of D-amino acid function among metazoans,” says Sasakura.

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Authors of the study believe their breakthrough modelling on ‘active matter’ could mark a turning point in the design of robots. With further development of the concept, it may be possible to determine the shape, movement and behaviour of a soft solid not by its natural elasticity but by human-controlled activity on its surface.

The surface of an ordinary soft material always shrinks into a sphere. Think of the way water beads into droplets: the beading occurs because the surface of liquids and other soft material naturally contracts into the smallest surface area possible — i.e. a sphere. But active matter can be designed to work against this tendency. An example of this in action would be a rubber ball that’s wrapped in a layer of nano-robots, where the robots are programmed to work in unison to distort the ball into a new, pre-determined shape (say, a star).

It is hoped that active matter will lead to a new generation of machines whose function will come from the bottom up. So, instead of being governed by a central controller (the way today’s robotic arms are controlled in factories), these new machines would be made from many individual active units that cooperate to determine the machine’s movement and function. This is akin to the workings of our own biological tissues, such as the fibres in heart muscle.

Using this idea, scientists could design soft machines with arms made of flexible materials powered by robots embedded in their surface. They could also tailor the size and shape of drug delivery capsules, by coating the surface of nanoparticles in a responsive, active material.. This in turn could have a dramatic effect on how a drug interacts with cells in the body.

Work on active matter challenges the assumption that the energetic cost of the surface of a liquid or soft solid must always be positive because a certain amount of energy is always necessary to create a surface.

Dr Jack Binysh, study first author, said: “Active matter makes us look at the familiar rules of nature — rules like the fact that surface tension has to be positive — in a new light. Seeing what happens if we break these rules, and how we can harness the results, is an exciting place to be doing research.”

Corresponding author Dr Anton Souslov added: “This study is an important proof of concept and has many useful implications. For instance, future technology could produce soft robots that are far squishier and better at picking up and manipulating delicate materials.”

For the study, the researchers developed theory and simulations that described a 3D soft solid whose surface experiences active stresses. They found that these active stresses expand the surface of the material, pulling the solid underneath along with it, and causing a global shape change. The researchers found that the precise shape adopted by the solid could then be tailored by altering the elastic properties of the material.

In the next phase of this work — which has already begun — the researchers will apply this general principle to design specific robots, such as soft arms or self-swimming materials. They will also look at collective behaviour — for example, what happens when you have many active solids, all packed together.

This work was a collaboration between the Universities of Bath and Birmingham. It was funded by the Engineering and Physical Sciences Research Council (EPSRC) through New Investigator Award no. EP/T000961/1.

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“I’m aware of no other documented case in which the invasion rate of a large aquatic system has been suppressed through a management intervention,”said Ricciardi. “This layer of protection is clearly beneficial. There are many highly invasive freshwater species in Europe, for example, that could be delivered in ballast water and would almost certainly proliferate in the Great Lakes. The regulation is likely preventing their introduction.”

The world’s most invaded freshwater ecosystem

No other freshwater ecosystem on Earth has been invaded as much, or as frequently, as the Great Lakes basin. Nearly 190 non-native species of fish, invertebrates, plants, plankton, and microbes have established populations in the basin over past two centuries. Nearly 65% of invaders recorded since the opening of the St Lawrence seaway in 1959 were transported to the Great Lakes in the ballast tanks of ships from overseas ports. These include notorious stowaways such as the zebra mussel, the quagga mussel, the spiny water flea, and the round goby — each among the most ecologically and economically damaging invaders in the basin.

Between 1959 and the mid-2000s, one new invader was discovered established in the Great Lakes every 6-7 months.

This onslaught prompted a move by Canada and the USA to harmonize regulations and mandate flushing saltwater through ballast tanks of all ships while they were still in open ocean, before entering the St Lawrence seaway bound for the Great Lakes. Saltwater flushing has been shown in experiments to cause a massive reduction in the abundance and variety of freshwater organisms carried in ballast tanks.

Empirical evidence of an abrupt reduction in invasion risk

The true test of such a regulation is its effect on the observed rate of species invasion. Since 2008, invasions reported in the Great Lakes basin have declined by 85% and are now at their lowest rate in two centuries. Other factors could have contributed to the abrupt decline in the invasion rate, but empirical evidence points to ballast water regulation as the overwhelming primary cause.

Although the Great Lakes remain vulnerable to invasions from poorly regulated sources, such as trade in living organisms (e.g. aquarium pets, live bait, ornamental garden plants, food markets), this study highlights the potential benefit of an internationally coordinated, evidence-based control strategy.

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