Is A Universal, One Dose Cholera Vaccine Possible?

The Gram negative bacterium, Vibrio cholerae (Vc) causes cholera, an enteric disease that has killed untold numbers of humans. In the 19 th century, whole-cell (W-C) cholera vaccines were tested in humans. Field trials (1960s70s) of injected, killed W-C (kW-C) Vc showed cholera-specific immune responses (antibodies, Abs) could be induced with a single dose in certain cohorts, but more durable immunity was sought with oral cholera vaccines. Newer, killed (two doses) and later modified live (one dose) W-C cholera vaccines for oral delivery were developed and extensively tested. After over 200 years, no consensus exists as to what are protective Vc antigens or how to identify them. An enduring cholera vaccine for children <5 years of age and Vc-antigen naïve individuals is still needed. The cholera outbreak in Haiti underscores some unresolved issues associated with the current cholera vaccines. Annually, is there enough cholera vaccine for those who need it? Who needs to be vaccinated and when? Given the displacement of populations during flooding like in Pakistan or in Haiti due to an earthquake, can a single dose of the kW-C cholera vaccine function to prevent or to contain an outbreak? What does ‘working’ entail: solely preventing deaths, or that plus long term immunity? Can a single formulation of Vc antigens be used for endemic or epidemic cholera which may require reactive vaccination for epidemics, but prophylactic vaccination for endemic cholera? The immunologic realities given the logistic issues for the different needs of a cholera vaccine are discussed.