Cellular antacids give vaccines a boost

Scientists in Italy have found that a drug that blocks acid buildup inside cells revs up the immune response to vaccines. Reporting in the September 19 issue of The Journal of Experimental Medicine, Vincenzo Barnaba and his team at the University of Rome show that people receiving booster shots against hepatitis B virus developed more robust immune responses if given a widely used anti-malaria drug called chloroquine.

Many vaccines are made up of soluble proteins derived from dangerous viruses or bacteria. But because of the way these proteins are broken down by cells, they do a poor job of prodding killer cells called cytolytic T cells into action. Cytolytic T cells are responsible for identifying and executing infected cells, so finding ways to get more of these cells activated is an important goal for vaccine development.

Barnaba and his colleagues now show that exposing cells to chloroquine prevents the acidification of cellular compartments into which vaccine proteins are taken up. Normally these proteins would be digested rapidly inside the compartment, but this is prevented by chloroquine because the degradation requires an acidic environment. The chloroquine treatment also made the vesicles leaky, allowing the proteins to escape into the cytoplasm of the cell. From there, they could be broken down such that small pieces of the protein are displayed to nearby cytolytic T cells; recognition of these small pieces of protein activates the killer cells.

The demonstration that a single dose of chloroquine boosted hepatitis B virus-specific T cell responses in up to 70% of vaccine recipients suggests that this readily available, oral drug might be a promising vaccine supplement.

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