Intranasal COVID-19 Vaccine Reduces Disease Severity and Blocks Transmission

Lancaster University Scientists have developed a COVID-19 vaccine that can be delivered via a nasal spray. In a preclinical trial, the vaccine was found to decrease both disease severity and transmission of the virus. The study results are published in the journal iScience.

Nipping SARS-CoV-2 "in the bud"

There are several vaccines authorized for human use against SARS-CoV-2, all of which are administered via intramuscular injection. These vaccines have proven highly effective in reducing the risk of severe COVID-19 disease and death, saving many lives across the globe. While a sore arm is a small price to pay for immunization against an infectious disease, the COVID-19 vaccine research landscape continues to evolve, and novel vaccine formats are being developed to improve our response against the virus further.

Intranasal vaccines are an example of an alternative approach for vaccination. Researchers at the University of Lancaster have been working in collaboration with scientists at the Texas Biomedical Research Institute to develop an intranasal vaccine against SARS-Cov-2.

Intranasal vaccines offer several advantages over the currently authorized vaccines, including the potential to block viral transmission. The next generation of COVID-19 vaccines must be able to stop transmission of the virus in individuals that have already been vaccinated, Dr. Muhammad Munir, virologist at the University of Lancaster, told Technology Networks.  

How can an intranasal vaccine achieve this? Let's take a step back and look at how SARS-CoV-2 infects the body. The virus initiates its infection in the cells that line our respiratory system, where it produces millions of progeny and triggers a cascade of replication. This process takes place in a very short time frame, and once the infection spreads, it's hard to get under control. "If we can train the cells that line our respiratory system against the virus, they will be better equipped to tackle the virus before it starts its infection," Munir explained. The intranasal vaccine essentially "nips SARS-CoV-2 in the bud": the virus is cleared before infection is established, therefore reducing transmission of the virus to others.

Intranasal vaccine effective in preclinical testing

The intranasal vaccine developed by Munir and colleagues is based on a bird virus known as Newcastle disease virus (NDV), which is harmless to humans. Munir, who is the leader of the research team, explained how the vaccine is created: "We took a SARS-CoV-2 antigen and incorporated it into a NDV such that it acts as a surrogate and presents the antigen to our immune cells. Since the NDV is harmless to us, it provides a mirror image of SARS-CoV-2 and trains our immune system to fight the virus if an individual gets exposed to SARS-CoV-2."

In a pre-clinical study, the vaccine was tested in both mice and hamster models. High levels of neutralizing IgA and IgG2a antibodies were detected, alongside T cell-mediated immunity when two doses were administered. In hamsters, the same dosage was found to reduce SARS-CoV-2 shedding significantly in nasal turbinate and the lungs, demonstrating its ability to halt the infection at the site of inoculation. This should offer both protection against clinical disease and transmission of the virus between individuals.

"Vaccine administration up in the nose usually elicits a local immune response that is sufficient  to curtail the virus at the site it starts its journey. We noticed a marked reduction of SARS-COV-2 replication in our pre-clinical studies even with one dose. However, better protection was noticed with two doses. Therefore, we aim to test single and double doses in human trials to understand the best vaccination scenario," Munir explained.

Variants of the virus continue to emerge across the globe and are cause for concern when it comes to vaccine efficacy. How might this intranasal vaccine perform against variants? "The intranasal vaccine in pre-clinical studies produced antibodies that can neutralize several important variants in laboratory experimentation. Given the nature of the vaccine and technology involved, we expect the induction of immunity against current or future variants," Munir said.

A mission to scale-up and fight vaccine inequality

The COVID-19 pandemic has emphasized the inequalities that exist across different parts of the world when it comes to accessing healthcare and preventatives such as vaccines. The team note that a unique feature of the intranasal vaccine is its economical and sufficient production in chicken eggs, adopting the same infrastructure that is used to produce influenza vaccines. "There are over 50 centers globally, including many in low- and middle-income countries, that are producing influenza vaccines and are used for only a few months in a year," Munir said. "We aim to exploit these production centers to scale-up this vaccine during the time these facilities are not producing influenza vaccine, which will significantly reduce the cost, and can enable the production of millions of doses without additional resources, manpower and training."

NDV is also stable at room temperature for weeks, and administration of a nasal vaccine requires little expert training, further reducing associated costs. The team emphasize that this makes the vaccine economical, scalable and deployable.

In terms of the next steps, the vaccine is heading for human clinical trials. However, this process is not without its challenges and financial burdens. "While immediate emphases on reducing hospitalization and death using COVID-19 vaccines remained evident, funding bodies (public and private) need to support technologies that can block transmission so that a realistic tool can be put in place to end the pandemic," said Munir.

"The vaccine offers hopes to people with medical conditions, who are needle phobic and people in deprived communities. We are preparing the clinical material and demonstrating its safety and stability to be used in clinical trials which we aim to start in the coming months," he concluded.

Dr. Muhammad Munir was speaking to Molly Campbell, Science Writer for Technology Networks.

Reference: Park J-G, Oladunni FS, Rohaim MA, et al. Immunogenicity and protective efficacy of an intranasal live-attenuated vaccine against SARS-CoV-2. iScience. doi: 10.1016/j.isci.2021.102941.