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

Vaccine. 2017 Feb 1;35(5):716-721. doi: 10.1016/j.vaccine.2016.12.067. Epub 2017 Jan 5.


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 5-17month but not the 6-12week age group, of delayed and variable meningitis onset after vaccination, and multiple etiologies. For both meningitis and cerebral malaria, the 5-17month 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 6-12week group, the control population in the 5-17month 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.

Keywords: Adverse events; Central nervous system infection; Immunization; Malaria; Meningitis; Non-specific effects; Rabies; Safety; Vaccine.

Publication types

  • Review

MeSH terms

  • Clinical Trials as Topic
  • Female
  • Humans
  • Immunization Schedule
  • Infant
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / adverse effects*
  • Malaria, Cerebral / diagnosis*
  • Malaria, Cerebral / immunology
  • Malaria, Cerebral / parasitology
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / parasitology
  • Malaria, Falciparum / prevention & control*
  • Male
  • Meningitis / diagnosis*
  • Meningitis / etiology
  • Meningitis / immunology
  • Meningitis / pathology
  • Protective Factors
  • Rabies / immunology
  • Rabies / prevention & control*
  • Rabies / virology
  • Rabies Vaccines / administration & dosage*
  • Vaccination*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects*


  • Malaria Vaccines
  • RTS,S-AS01 vaccine
  • Rabies Vaccines
  • Vaccines, Synthetic