Could the RTS,S/AS01 meningitis safety signal really be a protective effect of rabies vaccine?

The RTS,S/AS01 malaria vaccine has been associated with meningitis and cerebral malaria safety signals. Key characteristics of the meningitis signal include presence, in the 5–17 month but not the 6–12 week age group, of delayed and variable meningitis onset after vaccination, and multiple etiologies. For both meningitis and cerebral malaria, the 5–17 month old age group control arm had abnormally low incidences while other arms in both age groups had meningitis and cerebral malaria incidences similar to background rates. No single hypothesis postulating an adverse effect from RTS,S/AS01 unites these observations. Unlike the 6–12 week group, the control population in the 5–17 month old age group received rabies vaccine. This raises the possibility that non-specific rabies vaccine effects had a protective effect against central nervous system infection, a hypothesis consistent with the epidemiologic data. The lack of a confirmed biologic mechanism for such an effect emphasizes the need for additional studies.