ACE527 is a uniquely attractive vaccine candidate because:
• It is delivered orally: providing high acceptability and compliance.
• It has the potential to provide broad coverage: designed to generate an immune response to over 85% of ETEC strains.
• It has a dual mechanism of action: delivering strong immune responses to toxin and reducing bacterial colonization, thereby better promoting protection.
During the study, 29 subjects who had received the vaccine and 27 who had received an oral placebo were challenged with a virulent strain of enterotoxigenic E. coli. The study showed that:
• There was a reduction in the incidence and severity of diarrhoea (P = 0.04 and 0.06, respectively); vaccine recipients were more likely to be diarrhoea-free than placebo recipients after the challenge and vaccination resulted in approximately a 50% reduction in the number and amount of loose or liquid stools passed during the study period.
• The reduction in the total amount of diarrhoeal stool produced was most pronounced in the first 24 hours after the onset of symptoms (P = 0.05).
• There was a significant reduction in the level of colonization by the challenge bacteria (P = 0.001) as measured by bacterial shedding in the stool.
• The vaccine reduced the incidence of moderate-to-severe diarrhoea (P = 0.12).
“These results are very encouraging because the challenge consisted of a dose of bacteria much higher than what individuals are typically exposed to when they are naturally infected,” commented Ingelise Saunders, TD Vaccines’ CEO. “The oral formulation, dual mechanism of action, and broad spectrum coverage offered by ACE527 makes it a very attractive commercial opportunity. This is particularly the case because there is no ETEC vaccine currently available for travellers and no other ETEC vaccine currently in development has shown better protection in a challenge study. According to the World Health Organization, ETEC is endemic in over 150 countries, and around 10 million travellers are estimated to contract ETEC annually. We estimate that the ETEC vaccine market potential is €500 million. Our next step is to find a commercial partner with the skill set to fully capitalise on the vaccine’s potential.”
ETEC infection can lead to severe and debilitating diarrhoea, and each year the bacteria afflict millions of international travellers and children in the developing world. ETEC is responsible for an estimated 840 million gastrointestinal infections and about 380,000 deaths worldwide each year, the majority of which are young children in resource-poor countries.
The trial was conducted at the leading international centre for enteric vaccine evaluation in challenge trials, Johns Hopkins University, in Baltimore, Maryland. The development of ACE527 has been partially funded by PATH, an international nonprofit global health organisation that works on new vaccines for the developing world.