Scientists in Italy have found that a drug that blocks acid buildupinside cells revs up the immune response to vaccines. Reporting in theSeptember 19 issue of The Journal of Experimental Medicine, VincenzoBarnaba and his team at the University of Rome show that peoplereceiving booster shots against hepatitis B virus developed more robustimmune responses if given a widely used anti-malaria drug calledchloroquine.
Many vaccines are made up of soluble proteins derived from dangerousviruses or bacteria. But because of the way these proteins are brokendown by cells, they do a poor job of prodding killer cells calledcytolytic T cells into action. Cytolytic T cells are responsible foridentifying and executing infected cells, so finding ways to get moreof these cells activated is an important goal for vaccine development.
Barnaba and his colleagues now show that exposing cells tochloroquine prevents the acidification of cellular compartments intowhich vaccine proteins are taken up. Normally these proteins would bedigested rapidly inside the compartment, but this is prevented bychloroquine because the degradation requires an acidic environment. Thechloroquine treatment also made the vesicles leaky, allowing theproteins to escape into the cytoplasm of the cell. From there, theycould be broken down such that small pieces of the protein aredisplayed to nearby cytolytic T cells; recognition of these smallpieces of protein activates the killer cells.
The demonstration that a single dose of chloroquine boostedhepatitis B virus-specific T cell responses in up to 70% of vaccinerecipients suggests that this readily available, oral drug might be apromising vaccine supplement.
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