Researchers have developed an intranasal COVID-19 vaccine that enhances the immune system’s response to the virus, providing longer-lasting, greater protection than vaccine injections, even against new and emerging variants. The novel vaccine candidate could mean fewer boosters in future.
While the immediate threat of the COVID-19 pandemic has dissipated somewhat, with most returning to their pre-COVID lives, the continued rise of new virus variants means that vaccination is still necessary to protect the vulnerable in the community, such as the elderly and frail and those with pre-existing medical conditions.
Although many vaccines are available now that show protection in terms of significantly reducing infections, hospitalizations, deaths and virus transmission, breakthrough infections still occur, suggesting there are limitations to the duration of protection afforded by current vaccine regimes. So, in a study led by Duke-NUS Medical School in Singapore, researchers set about developing and testing a COVID-19 vaccine that’s delivered intranasally with the hope that it’s more effective.
“Our data show that, compared to subcutaneous vaccination, the intranasal route improved the response of certain immune cells, known as T cells, which reduced disease severity,” said Ashley St. John, corresponding author of the study. “Not only that, but it also resulted in a greater number of T central memory cells compared to subcutaneous vaccination, which could lead to longer-lasting protection.”
Given that SARS-CoV-2 infection is initiated at the mucosal surface of the nasal passages and lung airways, you’d expect that a vaccine delivered into the nose – right at the point where the virus enters the body – would be more effective than one injected into the skin or muscle.
As expected, the researchers found that after testing their vaccine candidate on hamsters, nasal administration boosted the antibody response in the mucosa. However, compared to subcutaneous vaccination, mucosal vaccination produced distinct effects on T cells and antibody responses.
Importantly, it produced longer-lasting mucosal and systemic immune protection against SARS-CoV-2 through the preferential induction of airway-resident T cells and central memory T (TCM) cells, which play a vital role in safeguarding the body when it's re-exposed to a virus. While antigen-specific TCMs were also present in the animals that received the subcutaneously administered vaccine and could be reactivated as expected, both their numbers and the magnitude of their cytokine production responses were heightened following mucosal vaccination. Cytokines are small proteins that are crucial in controlling the growth and activity of other immune and inflammatory cells.
The researchers’ use of adjuvants – substances that help create a stronger immune response – in the vaccine influenced the T cells’ characteristics, as well as their activation and cytokine production, with different adjuvants producing different T cell responses.
Further, immunoglobulin G (IgG), the most common antibody in humans and one that protects against bacterial and viral infections, was found to be more effective at neutralizing viral variants, including newly emerging ones, when induced through intranasal vaccination.
The improved response by T cells and IgG following intranasal vaccination provides evidence it contributes to greater and longer-lasting protection from SARS-CoV-2, which would limit vaccine breakthrough infections, the researchers said.
“While the acute phase of the pandemic may be behind us, the rise of new variants, including JN.1, which has triggered an increase in hospital admissions locally, demonstrates that we have room in our arsenal of vaccines and treatment for even better tools,” said Patrick Tan, one of the study’s co-authors. “This study shows that mucosal vaccination holds promise for improving COVID-19 vaccine efficacy with potentially fewer boosters needed.”
A patent has been filed that covers the invention of the vaccine composition formulated for intranasal delivery, paving the way for an industry partnership to potentially develop mucosal vaccines for COVID-19 and other pathogens that target mucosal surfaces.
The study was published in the journal eBioMedicine.
Source: Duke-NUS Medical School
