ABOVE: Vaccines against poxvirus and melanoma induced more memory T cells (shown) in mice when they entered through the lungs than when administered via another route.
FLICKR, NIAID

EDITOR’S CHOICE IN IMMUNOLOGY

The paper
K. Rakhra et al., “Exploiting albumin as a mucosal vaccine chaperone for robust generation of lung-resident memory T cells,” Sci Immunol, 6:eabd8003, 2021. 

Most vaccines are injected into muscle, where they induce systemic immunity. A goal of many vaccine developers is to engineer inhalable formulations that would build up powerful immunity localized in the mucous membranes that line organs such as the lungs. But to do so, vaccines need to breach that mucous membrane and head to the lymph nodes within the lungs, where they can instruct the immune system to generate memory T cells, key players in long-term immunity.

To accomplish that, Darrell Irvine, a biological engineer at MIT, and his team looked to albumin, a protein that naturally crosses mucous membranes. The researchers engineered a peptide vaccine against vaccinia (an animal poxvirus) with a lipid tail that binds to albumin and gave it to mice. As hoped, albumin shepherded the vaccine across the mucous membrane, transporting it into the lungs and lymph nodes, where it persisted for two weeks. 

When exposed to the virus, all of the mice that received the new vaccine intratracheally (to imitate an aerosolized vaccine for humans) survived, while those vaccinated with a standard vaccine or subcutaneously with the new vaccine all died.

The researchers also tested an albumin-binding vaccine against melanoma. When mice given this vaccine were later injected with melanoma cells to mimic metastases in the bloodstream, 8 out of 10 survived for 100 days, compared to 4 out of 10 that received a subcutaneous vaccine.

The key to the enhanced immunity was ensuring that the antigen stayed in the animals’ systems for at least two weeks, Irvine says. Standard peptide vaccines that lack a lipid tail typically degrade rapidly in vivo. “This suggests that any vaccine that promotes antigen/adjuvant persistence over such a timescale may be more effective for promoting protective T cell responses.”

“It will be particularly exciting” if the strategy works in humans, says Alistair Ramsay, a microbiologist at Louisiana State University who was not involved in the study.