Vaccine Helper Targets Muscle Cells

Vaccines are formulated with additives that enhance their immune-stimulating effects. Although these "adjuvants" have been used for many years, their mechanism of action and cellular targets remain unknown. Ennio De Gregorio, Rino Rappuoli, and coworkers at Novartis Vaccines & Diagnostics, in Siena, Italy, have used DNA microarray analysis to identify the genes affected by three types of adjuvants (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0804699105). Following injections in mouse muscle, the oil-in-water emulsion MF59, a common adjuvant in flu vaccines, induced changes in the expression of 891 genes, whereas CpG and alum, two other common adjuvants, affected only 387 and 312 genes, respectively. Some genes were modulated only when MF59 and CpG were administered together. The researchers identified 168 "adjuvant core-response genes" affected by all three adjuvants. These core genes regulate the expression of molecules that are usually associated with inflammatory responses. MF59 induced stronger and faster immune responses than CpG or alum. The researchers discovered two biomarkers that they used to identify muscle cells as the primary target of MF59.