Guillain Barre syndrome antibodies during Zika and Cikungunya vaccine trials

There is considerable concern over human viral infections caused by Zika virus and Chikungunya virus. In 2016 the WHO declared Zika a 'Public Health Emergency of International Concern,' flagging up specifically the lack of vaccines and of reliable diagnostic tests. Both infections are spread by Aedes egyptii mosquitoes. Zika infection is thought to be asymptomatic in a majority of exposed individuals, to cause symptoms such as rash and conjunctivitis in about 20% and is more rarely associated with neurological symptoms, including microcephaly in the newborn and Guillain-Barré syndrome (GBS) in adults. GBS can follow a number of infections (or, occasionally, vaccinations) including also Chikungunya. GBS is an acute paralysis seen as weakness that can affect breathing as well as the arms, legs and face. The mechanism is poorly understood but is believed to involve cross-reactive antibody targeting of glycolipid structures common to the the microbial pathogens and the human nervous system. It has been hard to develop widely applicable diagnostic tests and GBS is commonly diagnosed on the clinical assessment of a neurologist. The broad case for improved diagnostic platforms for GBS is readily made, but the need is all the more pressing in light of the current and forthcoming roll-out of new vaccine trials in regions most impacted by Zika and Chikungunya. A large number of Zika candidate vaccines are entering trials, these based on diverse approaches including viral recombinant subunit vaccines, live attenuated vaccines, whole inactivated vaccines and DNA vaccines. It is unknown whether any of these vaccines could cause GBS in some recipients as in 1976 when there was an increased risk of GBS after swine flu vaccination. A key concern voiced by vaccine producers is that any enhancement of such adverse events in Zika or Chikungunya vaccine trials would have devastating impact, including that on conduct of subsequent trials and implementation of related vaccines. However, we lack the tests for high-throughput diagnostic analysis and currently lack even basic disease surveillance on the seroprevalence of these GBS antibodies in the test populations. Here we bring together synergistic teams to harness neuroimmunologists with strong ZIka collaborations in Brazil, a glycobiology research team with unique resources for high-throughput analysis of glycoarray libraries with the wherewithal to translate GBS biosignature discovery into a simple, affordable kit. We see our technology as offering a safety-net to underpin development of Flavivirus vaccination programmes. We will start with a Discovery Phase, using GBS cohort sera to progress from comprehensive gylcolipid array libarary screening to a diagnostic probe set of high senstivity and specificity, which can be developed during the Development/Implementation Phase into a simplified, commercially affordable GBS diagnostic. The work is of high relevance to LMIC countries and will be conducted in collaboration with researchers in highly affected regions of Brazil.