Development of vaccines have come a long way since their inception in the late 18th century, leading to a medical revolution. According to estimates from the World Health Organization, vaccines have saved over 150 million lives worldwide.
Vaccination typically happens through an injection in the arm. This method protects the body against infections by mimicking the virus or bacteria one is vaccinated against. This prompts the immune system to produce antibodies that can combat the targeted pathogen.
Researchers at the University of Oslo and Oslo University Hospital have developed a novel technological platform for the development of vaccines.
“Our technology can be used to design subunit vaccines against almost any infectious disease. However, to develop a tailored vaccine, we need to identify which part of a protein from a virus or bacterium that it is strategic to focus the immune response towards,” Professor Jan Terje Andersen explains.
Infections often begin on the mucosal surfaces
Vaccines based on the new technology is administered not via invasive injections, but via the mucosal surfaces in the nose or mouth, either as a nasal spray or via an inhaler.
The mucosal surfaces play a crucial role in protecting the body against harmful substances, such as viruses and bacteria. A specialised type of polarizing epithelial cells forms tight barriers.
However, it is at the mucosal surfaces that infections happen.
“Infections typically occur when viruses or bacteria establish themselves on the mucosal surfaces or manage to breach the barriers and enter the body. They then replicate and multiply,” Andersen explains.
“If they are smart enough to avoid being destructed by the immune system, you could become seriously ill,” he adds.
An urgent need for more effective vaccines
Given that infections often begin at the mucosal surfaces, there is a strong necessity for design of vaccines that offer effective protection against viruses and bacteria right at these initial points of contact.
“There is a significant demand for additional vaccine technologies that can facilitate engineering of more effective vaccines, especially those that provide protection at the mucosal surfaces,” the Professor states.
“It is therefore essential to develop vaccines specifically designed to provide protection at the mucosal surfaces, rather than mainly providing systemic protection like traditional vaccines primarily do, which is within the bloodstream and tissues,” Andersen continues.
Enhanced navigating across the mucosal barriers ?
The barriers at the mucosal surfaces are very selective and typically permit the entry of only specific proteins.
Andersen and his colleagues have spent several years researching how to direct protein-based vaccines through these barriers. They have investigated how the polarized epithelial cell barriers can be used as a gateway for delivery of a protein called albumin.
Albumin acts as a natural molecular taxi for nutrients, hormones, and waste products.
“We have been able to guide this albumin carrier to a cellular receptor expressed by the polarizing epithelial cells at the mucosal surfaces. Albumin is then actively transported across these barriers. In this way, albumin can be coupled to the subunit vaccine and be delivered into the body,” explains the Professor.
“We have also explored how biotechnological tools can be used to design a super variant of albumin, which we use as part of the tailored vaccines,” he adds.
The new vaccine technology provides protection against infections in mice
Thus far, Andersen and colleagues have tested the novel vaccine technology in a series of mouse studies.?
The comprehensive work revealed that the vaccine concept protected the mice from both infections by the coronavirus and influenza virus.
“We exposed the vaccinated mice to lethal doses of either the coronavirus or the influenza virus. The vaccines provided protection against both infectious diseases,” Andersen reports.
The mice received the vaccines via their nose.
“By targeting the vaccines to the nasal mucosal surfaces of the mice, they elicited a robust local immune response at the mucosal surfaces. This immune response generated significant quantities of two types of antibodies, known as IgA and IgG. These antibodies effectively combat the viruses,” he explains.
Comparing the albumin-based vaccine with an mRNA vaccine against the coronavirus
The researchers compared their new vaccine concept with an mRNA vaccine currently used to vaccinate against the coronavirus.
This new albumin-based vaccine proved to offer better protection at the mucosal surfaces.
“When we compared the mRNA vaccine against the coronavirus with our new albumin-based vaccine, only the vaccine we have developed resulted in generation of protective IgA antibodies at the mucosal surfaces in the lungs,” states the Professor.
In addition to the protection at respiratory mucosal surfaces, the new vaccine concept provided systemic protection, similar to that offered by the mRNA vaccine and other traditional vaccines.
The next milestone is to test the vaccine technology on humans
The researchers aim to further develop and test the new vaccine on humans.
“The data from our research is robust and highly promising. We have demonstrated in multiple studies that this novel versatile vaccine technology is effective. We are, therefore, motivated to advance the concept and develop it for human testing,” Andersen says.
“This must occur in collaboration with the industry but may also involve partnerships with public health authorities. There is a pressing need to establish preparedness for any potential new epidemic or pandemic that may happen in the near future,” the Professor adds.
The study represents an important contribution to mucosal vaccine development?
Andersen notes that several research groups and companies are striving to develop vaccines that provide enhanced mucosal immunity.?
However, the work has not been straightforward.
“Previously, we have not had enough in-depth knowledge to design tailored vaccines for effective delivery across the mucosal surfaces. This targeting is crucial for induction of immune responses that can ensure robust antibody response both systemically and locally at the mucosal surfaces,” Andersen explains.
“Our study reveals a unique protein-based vaccine strategy that has been developed based on an in-depth understanding of complex biology,” the Professor concludes.
The study is based on extensive collaboration within Andersen's research group. Aina Anthi, Anette Kolderup, and Malin Bern have been central to this work. Additionally, the study builds on collaboration with several other research environments, led by Gunnveig Gr?deland, Elias Tj?rnhage, as well as Fridtjof Lund-Johansen and Eline Benno Vaage.
The study is funded by UiO's innovation programme SPARK, the Research Council of Norway, Helse S?r-?st, and the Coalition for Epidemic Preparedness and Innovation (CEPI).
Andersen leads one of the research groups at the Centre of Excellence?Precision Immunotherapy Alliance (PRIMA).?
Reference
Anthi, A. K., Kolderup, A., Vaage, E. B., Bern, M., Benjakul, S., Tj?rnhage, E., ... & Andersen, J. T. (2025). An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models. Nature Communications, 16(1), 3999. Please find the original publication here.