The vaccine combines three technologies — immune focusing, self-assembling nanoparticles, and DNA delivery — into a single platform for the first time. In addition to its other advantages, the vaccine could be stored at room temperature, making it potentially easier to transport to remote or developing locations than existing mRNA vaccines, which require specialized cold storage.

“This is among the first next-generation vaccines that will have more advanced features and broader protection,” said Daniel Kulp, Ph.D., associate professor in the Vaccine & Immunotherapy Center at The Wistar Institute and corresponding author of the study.

The paper, “Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drive rapid and potent immunogenicity capable of single-dose protection,” was published in the journal Cell Reports.

Existing vaccines include an unmodifided receptor binding domain of SARS-CoV-2 spike protein. The new vaccine includes a rationally engineered receptor binding domain using computational and structure-based design methodologies. The energinered receptor binding domain blocks ‘immune distracting’ sites and can therefore elicit stronger levels of protective, neutralizing antibodies.

Researchers then used naturally self-assembling proteins to form nanoparticles which display these highly engineered immunogens. By arranging themselves into structures that resemble an actual virus, the nanoparticles are more easily recognized by the immune system and transported to the germinal centers, where they activate B cells which produce protective antibodies.

Using nucleic acid vaccine delivery technology similar to mRNA, the nanoparticle vaccine is encoded in DNA and delivered into cells thereby giving genetic instructions for the body to build the immunogen internally. This is an advance over traditional vaccines that must be manufactured in specialized factories through complex vaccine production processes. In contrast to other vaccines, Dr. Kulp noted that one advantage of the DNA platform is that it doesn’t require refrigeration and it can also be quickly reformulated to target new variants.

In animal models, researchers found that the DNA delivered immune-focused nanoparticle vaccine produced much higher levels of neutralizing antibodies than the vaccine that wasn’t immune-focused.

“A difficulty with current vaccines is that neutralizing antibodies decline over time,” Kulp said. The nanoparticle vaccine produced durable responses after a single immunization out to six months in mice, unlike what we are seeing with current SARS-CoV-2 vaccines in people.

The ultimate test for SARS-CoV-2 vaccine candidates is protection from death in SARS-CoV-2 challenge experiments. The researchers found that in a lethal challenge model 100% of mice who received the immune-focused nanoparticle vaccine were protected from death with a single low dose. Most mice who received the standard, non-immune focused vaccine died within 10 days of challenge.

The vaccine assessment was conducted in both wild-type mice and mice that were genetically engineered to mimic human immune systems, he noted.

Even without being updated, the immune-focused vaccine showed a comparable level of antibody production to Delta, and other variants, Kulp said. That’s partly because of the immune focusing approach itself, he noted; in blocking parts of the receptive binding domain for the purpose of inhibiting non-neutralizing antibodies, it also blocks many of the areas affected by spike protein mutations. Studies on the Omicron variant are underway.

Researchers are seeking funding to begin human trials of the vaccine.

Co-author David B. Weiner, Ph.D., executive vice president, director of the Vaccine & Immunotherapy Center and the W.W. Smith Charitable Trust Professor in Cancer Research, at The Wistar Institute, said the vaccine could provide a needed step forward to improve protection against COVID-19.

“Current vaccine effects on reducing transmission of SARS-CoV-2 variants of concern including Delta and Omicron could be improved for their breadth of protection as well as their immune potency,” Weiner said. “This study demonstrates that using a nucleic acid approach combined with in vivo structural assembly of a glycan immune-focused nanoparticle drives single protection and neutralization against diverse variants of concern in a dose-sparing formulation. Additional studies of this vaccine approach for SARS-CoV-2 appear timely and important.”

Co-authors: Kylie M. Konrath, Kevin Liaw, Yuanhan Wu, Xizhou Zhu, Susanne N. Walker, Ziyang Xu, Neethu Chokkalingam, Nicholas J. Tursi, Mansi Purwar, Emma Reuschel, Drew Frase, Benjamin Fry, and Ami Patel from Wistar; Katherine Schultheis, Igor Maricic, Viviane M. Andrade, Kate E. Broderick, Laurent M.P.F. Humeau, and Trevor R.F. Smith from Inovio Pharmaceuticals; Himanshi Chawla and Max Crispin from the University of Southhampton; Jianqiu Du and Alan Moore from Indiana University; Jared Adolf-Bryfogle and Jesper Pallesen from the Institute for Protein Innovation; Matthew Sullivan from the University of Pennsylvania; and Christel Iffland from Ligand Pharmaceuticals.

Work supported by: Wistar Coronavirus Discovery Fund and CURE/PA Department of Health grant SAP# 4100083104, COVID/PA Department of Human Services grant SAP# 4100089371, NIH/NIAID CIVICs grant 75N93019C00051, Wistar Coronavirus Discovery Fund, Wistar SRA 16-4 / Inovio Pharmaceuticals, COVID/PA Department of Human Services grant SAP# 410089371; Indiana University.

While for most of us cryptographic systems are things that just run “under the hood,” they are an essential element in the world of digital communications. However, the upcoming rise of quantum computers could shake the field of cryptography to its core. Fast algorithms running on these machines could break some of the most widely used cryptosystems, rendering them vulnerable. Well aware of this looming threat, cryptography researchers worldwide are working on novel encryption methods that can withstand attacks from quantum computers.

Chaos theory is actively being studied as a basis for post-quantum era cryptosystems. In mathematics, chaos is a property of certain dynamic systems that makes them extremely sensitive to initial conditions. While technically deterministic (non-random), these systems evolve in such complex ways that predicting their long-term state with incomplete information is practically impossible, since even small rounding errors in the initial conditions yield diverging results. This unique characteristic of chaotic systems can be leveraged to produce highly secure cryptographic systems, as a team of researchers from Ritsumeikan University, Japan, showed in a recent study published in IEEE Transactions on Circuits and Systems I.

Led by Professor Takaya Miyano, the team developed an unprecedented stream cipher consisting of three cryptographic primitives based on independent mathematical models of chaos. The first primitive is a pseudorandom number generator based on the augmented Lorenz (AL) map. The pseudorandom numbers produced using this approach are used to create key streams for encrypting/decrypting messages, which take the stage in the second and perhaps most remarkable primitive — an innovative method for secret-key exchange.

This novel strategy for exchanging secret keys specifying the AL map is based on the synchronization of two chaotic Lorenz oscillators, which can be independently and randomly initialized by the two communicating users, without either of them knowing the state of the other’s oscillator. To conceal the internal states of these oscillators, the communicating users (the sender and the receiver) mask the value of one of the variables of their oscillator by multiplying it with a locally generated random number. The masked value of the sender is then sent to receiver and vice-versa. After a short time, when these back-and-forth exchanges cause both oscillators to sync up almost perfectly to the same state in spite of the randomization of the variables, the users can mask and exchange secret keys and then locally unmask them with simple calculations.

Finally, the third primitive is a hash function based on the logistic map (a chaotic equation of motion), which allows the sender to send a hash value and, in turn, allows the receiver to ensure that the received secret key is correct, i.e., the chaotic oscillators were synchronized properly.

The researchers showed that a stream cipher assembled using these three primitives is extremely secure and resistant to statistical attacks and eavesdropping since it is mathematically impossible to synchronize their own oscillator to either the sender’s or the receiver’s ones. This is an unprecedented achievement, as Prof. Miyano states: “Most chaos-based cryptosystems can be broken by attacks using classical computers within a practically short time. In contrast, our methods, especially the one for secret-key exchange, appear to be robust against such attacks and, more importantly, even hard to break using quantum computers.”

In addition to its security, the proposed key exchange method is applicable to existing block ciphers, such as the widely used Advanced Encryption Standard (AES). Moreover, the researchers could implement their chaos-based stream cipher on the Raspberry Pi 4, a small-scale computer, using Python 3.8. They even used it to securely transmit a famous painting by Johannes Vermeer between Kusatsu and Sendai, two places in Japan 600 km apart. “The implementation and running costs of our cryptosystem are remarkably low compared with those of quantum cryptography,” highlights Prof. Miyano, “Our work thus provides a cryptographic approach that guarantees the privacy of daily communications between people all over the world in the post-quantum era.”

With such power of chaos-based cryptography, we may not have much to worry about the dark sides of quantum computing.

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Materials provided by Ritsumeikan University. Note: Content may be edited for style and length.

They found that the set up could produce around 45 Mega-Watt hours per year, which accounts for roughly 35% of the Abbey’s annual usage. The equivalent amount of carbon dioxide saved, versus buying the electricity from the National Grid, would be around 10 tonnes per year, significantly reducing the carbon footprint of the building.

A cost-benefit analysis showed that the system could pay for itself in 13 years and provide a profit of £139,000 over a lifespan of 25 years. It would also future-proof the Abbey from rising costs of energy bills. The findings show that despite a large initial outlay, the system would be financially feasible for the historic grade I listed building.

They have published their findings in the journal Energy Science & Engineering.

Matthew Smiles, PhD researcher at the University of Liverpool who is first author on the study, said: “It’s very difficult to insulate historic Grade I listed buildings like Bath Abbey, so installing solar panels is a good way to reduce the carbon footprint of these buildings.

“Most of the Abbey’s electricity is used during the day, when the solar panels would be generating energy from sunlight, making it an ideal building to implement them.

“With increasing energy prices, installing solar panels could result in large cost savings.”

In the model, the panels were sited such that they couldn’t be seen from the street, only from a distance from the Bath Skyline, so would have minimal visual impact on the historic building.

Professor Alison Walker, Director of the Centre for Doctoral Training in New and Sustainable Photovoltaics at the University of Bath’s Department of Physics, has collaborated with Bath Abbey for several years on the project.

She said: “This paper is an amazing collaboration between the PhD students and the Bath Abbey Footprint Project who first invited us to look into solar for the Abbey and arranged for the students to visit the Abbey roof to see how solar could work.

“It’s great for the students, whose research projects are all on solar power, to see a practical application of the training they have done in universities across the UK.”

PhD student Adam Urwick, who performed the abbey modelling, module design and shadings analysis from the University of Sheffield, said: “The proposed installation would generate 45MWh and save about 10 tonnes of CO2 emissions in its first year of generation. This is equivalent to the emissions of an average vehicle driving 80,000km — almost twice the circumference of the Earth.

“Not only does it make financial sense, but the installation of solar panels on Bath Abbey could inspire reinvigoration of solar PV deployment in the UK which has stagnated over the past 5 years.”

The research was performed as part of a feasibility study for the Abbey’s Footprint programme, as part of the Church of England’s campaign, Shrinking the Footprint, which aims to reduce the carbon footprint of its historic buildings.

The Bath Abbey Footprint programme has already reduced its carbon footprint by using the geothermal hot springs of the local area to provide underfloor heating and installing LED light bulbs to illuminate the interior.

Although environmental and planning rules must also be considered carefully, installing solar panels is another potential way the Abbey could reduce its footprint further.

Nathan Ward, Footprint Project Director at Bath Abbey, said: “It’s been fantastic working with the University of Bath and the other universities on this project. The students and staff have shown a high level of commitment, knowledge and enthusiasm and have provided us with well-considered and invaluable research that we would like to use practically in the future.

“The research will help us greatly in exploring the use of solar panels on the Bath Abbey roof. The Abbey is highly committed in the outstanding care of both our built and natural environment and to reduce our carbon footprint.

“This has been achieved in part thanks to our Footprint project which saw the installation of new LED lighting and eco-friendly underfloor heating that uses energy from Bath’s natural hot water, but the use of solar panels would enable us to reduce our carbon footprint further.”

The Centre for Doctoral Training in New and Sustainable Photovoltaics is a consortium of seven universities and 12 industrial partners led by the University of Bath and funded by the Engineering and Physical Sciences Research Council (EPSRC). The universities include: The Universities of Bath, Cambridge, Liverpool, Loughborough, Oxford, Sheffield and Southampton.