Scientists have been aiming to develop an effective vaccine against Shigella, one of the most common bacterial organisms causing serious diarrhea over a hundred years. After a long time of work, this endeavor looks to have reached the most promising stage to date. The new experimental oral vaccine candidate WRSs2 protected 89 percent of subjects in a rigorous clinical trial, bringing hope that finally there might be an armament against this obstinate pathogen. The research was published in The Lancet Infectious Diseases (Sclar et al.
2007). It was a phase 2 trial, involving 108 healthy subjects, with the individuals brought to Cincinnati Children’s Hospital Medical Center and the Hope Clinic at Emory Vaccine Center in Atlanta. The researchers tested the live-attenuated form of Shigella sonnei, which was administered orally as a liquid to be swallowed. Following two injections, the study subjects were administered the full dose of bacteria.
The study was performed under medical supervision, with very few vaccinated individuals suffering from shigella symptoms, where almost all those receiving a placebo exhibited clear symptoms (such as diarrhea and fever). Protection levels are exceptional. Previous vaccine candidates did not come close to this level of efficacy. They gave some protection in adults but not children (e.g. S.8A/8F) or gave lukewarm results overall, increased side-effects (e.g.
Water Virus/Pt/7-74) or gave very good results but were too unsafe (e.g. WRSs1). WRSs2 achieved higher protection but remained acceptably safe (mild diarrhea and head-ache reported in >50%, but no one was hospitalized In particular for the vaccine) Shigella exacts a significant human toll. While globally there are tens of millions of shigella cases each year, the bacteria is also responsible for hundreds of thousands of deaths, predominantly in kids under five years old in low- and middle-income nations. Symptoms can escalate quickly from copious watery diarrhea to dysentery, fevers and life threatening dehydration. While antibiotics have long been used for treatment, resistance levels have risen above 80percent for some drugs in some places, reducing treatment options. A vaccine to prevent infection would have a huge impact.
The trial used the strain of Shigella sonnei, which may be more tied to travel, military, and daycare center strains, and outbreaks in high income countries. The researchers stress that the single most important next step is to test the vaccine in those who need it most in young children in endemic areas. The more extensive trials will also enable spacing of doses to be fine-tuned and to assess safety in different populations. What is truly remarkable about this advance is that for over thirty years, no licensed vaccine has been available for Shigella despite relentless effort.
The invasive nature of the bacteria and their continually changing surface make them notoriously difficult to develop vaccins against. WRSs2 is based on a finely tuned attenuated live bacteria to elicit protection in the absence of disease. The impressive benefits seen in a challenge study gives confidence that the method is worth developing.
