Anyone who lived through the first year of the COVID-19 pandemic remembers that they – and Third World countries and even the US – were ready to beg, borrow, or steal to get Pfizer or Moderna vaccines to save them. Even prime ministers and presidents were involved in making deals to get the shots for their populations.
Some 13.5 billion doses were sold and injected. These vaccines have played a huge role against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by making possible the rapid scale-up production and manufacturing of a synthetic vaccine while controlling the severity of the disease.
But not anymore. Researchers at Tel Aviv University say they have developed an effective, inexpensive, and simple COVID-19 vaccine that can be stored at room temperature and administered as a nasal spray. This global breakthrough shatters the duopoly in which the two companies controlled the supplies.
Prof. Ronit Satchi-Fainaro’s lab at TAU’s Faculty of Medical and Health Sciences collaborated with Prof. Helena Florindo’s lab at the University of Lisbon in Portugal to produce a novel nanovaccine for COVID-19. They maintain that the vaccine, comprised of 200-nanometer particles, trains the immune system against all common variants just as effectively as existing vaccines. Other co-first authors of the study were Rita Acurcio, Daniela Vaskovich-Koubi, and Ron Kleiner.
Moreover, unlike other vaccines, it is conveniently administered as a nasal spray and does not require a cold supply chain or ultra-cold storage. These unique features pave the way to vaccinating Third World populations and developing simpler, more effective, and less expensive vaccines in the future. The revolutionary study was featured on the cover of Wiley’s prestigious journal Advanced Science under the title “Intranasal Multiepitope PD-L1-siRNA-Based Nanovaccine: The Next-Gen COVID-19 Immunotherapy.”
COVID-19 nanotechnology
THE FIRST approved vaccines for human use against COVID-19 are based on nanotechnology, but although they are quickly manufactured, modular, and can reduce disease severity, the vaccines that are now available are limited in preventing infection. Thus, there has been a demand around the world for new and effective preventive vaccine technologies.
The team set out to develop a flexible nanovaccine platform for a nasal spray to trigger mucosal immunity, which is fundamental for optimal protection against respiratory virus infection.
The next-generation multiepitope nanovaccines co-deliver immunogenic peptides, selected by an interface between computer science and experimental immunology, along with adjuvants (additional chemicals to enhance the body’s immune response) and regulators of the PD-L1 expression.
They focused on SARS-CoV-2 peptides as relevant antigens to validate the approach to evoke both local and systemic cellular- and humoral-specific responses against the virus. This led to the secretion of immunoglobulin A (IgA), capable of neutralizing SARS-CoV-2, including variants.
Since the need to refrigerate ordinary vaccines is mandatory, it was a major benefit that the lyophilized nanovaccine is stable for the long-term at room temperature and retains its efficacy when it’s reconstituted with liquid. This makes it particularly relevant for developing countries and offers a modular system adaptable to future viral threats.
The pfizer and Moderna vaccines, approved by the European Medicine Agency (EMA) and the US Food and Drug Administration (FDA), are composed of messenger ribonucleic acid (mRNA) to enable protein production by host cells. These nanotechnology-based vaccines hold several advantages over traditional vaccination approaches, but they pose several challenges such as high manufacturing, handling, and storage costs. The need for a vaccine that had to be refrigerated from production to the individual’s arm imposes significant logistical challenges.
Vaccines based on peptides, however, are stable in their freeze-dried form at room temperature, eliminating the need for cold chain storage and distribution.
“The new nanovaccine’s development was inspired by a decade of research on cancer vaccines,” Satchi-Fainaro explained. “When the COVID-19 pandemic began, we set a new goal: training our cancer platform to identify and target the coronavirus. Unlike Moderna and Pfizer, we did not rely on full protein expression via mRNA.
“Instead, using our computational bioinformatics tools, we identified two short and simple amino acid sequences in the virus’s protein, then synthesized them, and encapsulated them in nanoparticles,” she said. “Eventually this nanovaccine proved effective against all major variants of COVID-19, including Beta, Delta, Omicron, and the others.”
She said that the new nanovaccine “offers a significant advantage over existing vaccines because it is needle-free and administered as a nasal spray. This eliminates the need for skilled personnel such as nurses and technicians to administer injections, while also reducing risks of contamination and sharp waste. Anyone can use a nasal spray, with no prior training.”
Another major advantage of the revolutionary nanovaccine is its minimal storage requirements. Moderna’s sensitive mRNA-based vaccine must be kept at –20°C and Pfizer’s at –70°C, generating great logistic and technological challenges, such as shipping in special aircraft and ultra-cold storage – from the factory to the vaccination station. The new type has synthetic nanoparticles that are far more durable and can be stored as a powder at room temperature. “There’s no need for freezing or special handling,” the TAU professor noted.
“You just mix the powder with saline to create the spray. For testing purposes, as part of the EU’s ISIDORe (Integrated Services for Infectious Disease Outbreak Research) feasibility program, we shipped the powder at room temperature to the INSERM (National Institute of Health and Medical Research) infectious diseases lab in France. Their tests showed that our nanovaccine is at least as effective as Pfizer’s vaccine when needed,” Satchi-Fainaro said.
ISRAELI PUBLIC health expert Dr. Inon Schenker said “of course, any solution that is easy to implement is beneficial for immunization coverage,” when asked to comment.
Schenker, who at the high point of the pandemic was CEO of Impact Vaccination, a consultancy firm pre-qualified by COVAX for vaccination capacity-building and the Jerusalem Impact Vaccination Initiative that focused on faith-based organizations, promoted demands for the vaccine, community education and reducing hesitancy about vaccinating children, teens and adults against COVID-19.
“The development of vaccines that are easy to store without the need for cold chain logistics and are simple to administer with minimal risk of side effects is a critical step forward in global health preparedness,” he said. “A major viral pandemic requiring global mobilization, similar to COVID-19, is not just a possibility – it’s a reality for which we must be prepared. When approved by the FDA, TAU’s nanoparticle-based vaccine could be on target.”
Schenker added that “the most pressing challenge today in global public health and vaccination is addressing vaccine hesitancy, the collapsing trust of the public in health authorities and the alarming decline in routine childhood immunizations. This has already led to a resurgence of measles outbreaks worldwide. It is imperative to act on initiatives like the American Public Health Association’s policy recommendations and President Isaac Herzog’s collaboration with religious leaders in the Holy Land. Their efforts to unify voices in promoting vaccinations and enhancing trust are crucial and must be executed urgently and widely to safeguard future generations.”
TAU’s groundbreaking project has received competitive research grants from the Israel Innovation Authority and Merck under the Nofar program, as well as funding from Spain’s “La Caixa” Foundation Impulse as an accelerated program, and support from the ISIDORe feasibility program. It is also part of a broader vaccine platform development program at Satchi-Fainaro’s lab, supported by a European Research Council (ERC) Advanced Grant.