PLoS Pathog. 4, e1000138 (2008)

Immunologists have long known that inactivated whole-virus vaccines are superior to viral-subunit or split-virus vaccines. Anke Huckriede at the University of Groningen in the Netherlands and her colleagues show that for an H5N1 influenza vaccine this enhanced efficacy is due to the action of viral single-stranded RNA molecules. These stimulate the innate immune response, an arm of the immune system that responds quickly and boosts long-term immunity.

The team looked at Toll-like receptors (TLRs), proteins that often initiate innate immune responses. Mice lacking TLR7 — which recognizes the influenza virus's single-stranded RNAs — or other proteins in the same pathway had a degraded immune response to a whole-virus H5N1 vaccine.