Vaccination is one of the most effective public health measures, saving millions of lives annually. However, there is an urgent need for vaccines that are not only efficient but also provide protection at the sites where infections begin, particularly at mucosal surfaces such as those in the respiratory tract. Traditional vaccines are typically administered intramuscularly or subcutaneously, and while they are effective at generating systemic immune responses, they often fail to induce strong immunity at mucosal entry points.
A recent study published in Nature Communications by Professor Jan Terje Andersen and colleagues introduces a novel vaccine technology that addresses this challenge. The researchers developed a vaccine platform in which a subunit antigen is genetically fused to albumin, a naturally abundant protein in the body. Albumin was selected as the carrier molecule due to its interaction with the neonatal Fc receptor (FcRn), which is expressed on mucosal epithelial cells and plays a key role in transporting albumin across mucosal barriers.
The vaccine was administered intranasally in several mouse models and was shown to induce both systemic and mucosal antigen-specific antibody responses. Importantly, mice vaccinated with the albumin-antigen fusion were protected against infection by respiratory viruses, including SARS-CoV-2 and influenza A. The inclusion of an adjuvant further enhanced the immune response and could be conjugated directly to the albumin molecule for site-specific delivery.
When compared with other vaccine formats, such as an intramuscular mRNA vaccine and an intranasal vaccine using a carrier of similar molecular size, the albumin-based vaccine was the only one to elicit a robust mucosal IgA response. This is a significant finding, as IgA antibodies are critical for neutralizing pathogens at mucosal surfaces, which serve as the primary entry points for many respiratory viruses.
The study also highlights the importance of the engineered human albumin variant used in the platform. This variant demonstrated an enhanced ability to engage with FcRn, promoting efficient transport across mucosal barriers and subsequent immune activation. The researchers carefully designed their preclinical studies to account for cross-species differences in FcRn binding, ensuring the relevance of their findings for future human applications.
A study by Susan Park Ochsner demonstrated that intranasal immunization with a hemagglutinin-Fc fusion protein (HA-Fc) and CpG adjuvant conferred significant protection against lethal influenza A virus challenge in mice. This protection was dependent on FcRn-mediated transport, as FcRn knockout mice did not exhibit the same immune response. The vaccine induced high levels of neutralizing antibodies, robust B and T cell responses, and reduced lung inflammation.
Overall, the intranasal, albumin-based vaccine platform presents a promising approach for developing vaccines that provide strong systemic immunity along with targeted protection at mucosal sites. This needle-free strategy could be especially valuable in preventing respiratory infections caused by viruses that pose serious global health threats.
References
- An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models | Nature Communications [Internet]. [cited 2025 May 2]. Available from: https://www.nature.com/articles/s41467-025-59353-6
- Ochsner SP, Li W, Rajendrakumar AM, Palaniyandi S, Acharya G, Liu X, et al. FcRn-Targeted Mucosal Vaccination against Influenza Virus Infection. J Immunol. 2021 Sep 1;207(5):1310–21.