Better vaccine targeting: study identifies key mechanism

A photo of a doctor giving an injection into a patient’s upper arm.
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In a study led by researchers at Yale and The Jackson Laboratory, investigators zeroed in on a specific cell type that is uniquely responsible for activating a strong response to vaccination. The insight could lead to changes in how vaccines are developed and delivered to maximize immunity to infections like the flu, said the researchers.

The findings are published in the journal Science Immunology.

Scientists had recently identified the type of immune cell that is key to generating an effective vaccine response, but the mechanism was not well understood. In this study, the research team investigated how the cells are “primed” and activated during immunization.   

Using mouse models, the team focused on dendritic cells, which alert the immune system to the presence of a vaccine. The researchers identified the particular type of dendritic cell (DC), known as a conventional type 2 DC, that processes and presents particles of a vaccine to the immune system’s T cells, ultimately activating the release of antibodies that block infections.

The insight could inform where in the body vaccines should be given in order to directly reach those dendritic cells. “What we believe is that when we’re vaccinating into the muscle, we’re probably not targeting the type 2 dendritic cells well,” said co-corresponding author Stephanie Eisenbarth, associate professor of laboratory medicine. “But if we deliver the same vaccine into the skin or the lung, the dendritic cells are right there, enabling a more potent vaccine response. Location is very important.”

The finding could also help researchers figure out how to effectively deliver vaccines at lower doses during pandemics, when vaccine supplies are stretched.

It’s important to determine how best to deliver vaccines,” said Eisenbarth. “During pandemics, we potentially can’t make enough flu vaccine to cover everybody in a short period of time. But if we could give one-tenth the dose, that could be very powerful.” Older epidemiological data studying vaccine responses in humans in fact concluded that injections in the skin rather than the muscle are much more potent, but the reason for this effect was not known.

The next steps in research are to further examine dendritic cells and how to best get vaccines to them. “If we do, we could potentially use a lot less vaccine to get the same level of antibody protection,” noted Eisenbarth.

Other study authors are J.K. Krishnaswamy, U. Gowthaman, B. Zhang, J. Mattsson, L. Szeponik, D. Liu, R. Wu, T. White, S. Calabro, L. Xu, M. A. Collet, M. Yurieva, S. Alsén, P. Fogelstrand, A. Walter, W.R. Heath, S.N. Mueller, U. Yrlid, and A. Williams.

This work was supported by the National Institutes of Health, The Hartwell Foundation Individual Biomedical Research Award, Hood Foundation Child Health Research Award, and the Agency for Science, Technology and Research Singapore. Authors Fogelstrand and Yrlid are shareholders and cofounders of Kromnigon AB. 

Citation: Science Immunology

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