When people think about vaccines, they picture a shot in the arm that trains the immune system to fight disease throughout the body. New research from Johns Hopkins University suggests that some vaccines may be doing something more precise: helping the immune system build protection in specific organs.
In a study led by Hai-Quan Mao, Director of the Institute for NanoBioTechnology and professor of materials science and engineering and biomedical engineering at Johns Hopkins University, researchers found that mRNA vaccines, used in COVID-19 vaccines, can travel beyond the injection site and modulate immune responses in organs such as the liver and lungs. In these tissues, they can generate localized protection that helps to fight against infections and the spread of cancer.
The team also discovered that where the vaccine travels, and where immunity forms, depends on how the vaccine is designed. By adjusting the molecular makeup of the lipid nanoparticles, including the types and ratios of lipids used to package and transport the mRNA, the researchers were able to influence how the particles moved through the body and which organs they reached.
The findings were published today in Nature Biomedical Engineering.
This study provides new insights into how mRNA LNP vaccines function in vivo and could significantly reshape current understanding of vaccine biodistribution and immune programming.
These vaccines rely on carriers called lipid nanoparticles, or LNPs, to deliver genetic instructions into cells. Scientists have long believed that after an injection, most of these particles stay near the muscle and in the lymph nodes. This study shows that some of them can enter the systemic circulation and reach other parts of the body and this movement is not random: it depends on how the nanoparticles are formulated.
“Our work shows that where a vaccine travels can shape where immune protection develops,” said Mao. “By engineering the lipid nanoparticles, we can begin to direct the immune responses towards organs where they may be needed the most.”
Some formulations accumulated in the liver, while others showed stronger activity in the lungs. These differences translated directly into where immune responses were strongest. The study highlights a key type of immune cell known as tissue-resident memory T cells. These specialized immune cells act like local guards, ready to respond quickly if disease appears in that organ. The team found that LNPs that trafficked to the liver generated strong liver-resident T cell responses and improved control of liver tumors in mouse models. Similarly, lung-biased formulations enhanced immune responses in the lungs and reduced metastatic tumor burden in mice.
“These tissue-resident immune cells are critical for fighting diseases at their point of entry,” said Christine Wei, a biomedical engineering PhD candidate and the study’s lead author. “This gives us a way to program immunity exactly where it’s needed, which adds an exciting new layer of control in the immunoengineering space.”
The team developed a large library of nanoparticle formulations and used it to identify designs that enhance organ-specific immune formation. Their results show that subtle changes in lipid composition can dramatically change how nanoparticles move through the body and where they activate immunity.
“While changing the nanoparticle formulation had a major effect on T-cell responses in specific organs, antibody responses remained largely unchanged,” said Yining Zhu, an INBT Postdoctoral Researcher who co-led the study. “That tells us we may be able to selectively program one part of the immune response without dramatically altering another.”
The findings challenge the conventional view that the movement of vaccine particles through the body is merely a side effect. Instead, the study shows that this systemic trafficking is an important part of how vaccines work and by better understanding and controlling this process, scientists may be able to design more precise and effective prophylactics and treatments.
“This opens up a new dimension in vaccine design,” said Mao. “Instead of just asking how strong the immune response is, we can now ask where that response should happen, and design for it.”
Looking ahead, the team is working to better understand the biological mechanisms that control how different nanoparticle formulations travel throughout the body and direct immune responses to specific tissues. By leveraging these insights, they aim to design next-generation mRNA vaccines that can deliberately direct protective immune responses to specific organs, improving protection against metastatic cancers and infectious diseases that target the liver, lungs, and other tissues.
