US company Avant Immunotherapeutics announced yesterday the initiation of a Phase II study on its typhoid fever vaccine candidate, Ty800, which would determine the optimal dosage for a single dose, oral vaccine for further development. The move marks a further step towards the company's goal of developing a "Super Combination Traveler's Vaccine" which would be designed as a single dose oral vaccine against multiple bacterial diseases including typhoid, cholera, enterotoxigenic E. coli (ETEC) and paratyphoid. While the super vaccine is some years off, Avant is progressing with several clinical trails that would be combined to produce the vaccine, which would be beneficial to travelers and mass vaccinations in the developing world. At present, Avant has developed a single dose, oral delivery platform based on genetically modified cholera or Salmonella typhi bacterium. The vaccine can be a stand-alone vaccine, with the genes encoding for toxicity spliced out but when administered, still generates an antibody attack but without the disease symptoms. Alternatively, the bacterium could act as a vector with genes encoding for antigens of a different disease being spliced into the areas where the toxic genes of the first disease have been removed, thereby providing protection against two diseases. Speaking to US-PharmaTechologist.com, Avant senior vice president and chief financial officer Avery Catlin said the company was hoping to be able to splice maybe three different diseases into the original bacterium vector backbone, but this was still to be studied. The Phase II study of Ty800 would be an important component in the development of the super vaccine, he said. A cholera vector containing ETEC genes will be Avant's first multi-valent vaccine to enter Phase I/II clinical trials, expected to be later this year. Meanwhile, a paratyphoid A vaccine using the Ty800 backbone is in preclinical trials. "The reason [a super vaccine is so attractive] is because this gives a broad coverage of enteric diseases that cause diarrhea and is competitive [in the market place] because it's a multi-valet vaccine," Catlin said. As individual vaccines, the single dose oral delivery platform is also attractive. Currently, there are two vaccines against typhoid fever: Crucell's Vivotif, a three to four dose oral vaccine; and Sanofi's Typhim-Vi, a single-dose, injectable product. "We believe a single dose, oral vaccine that gives rapid protection is an ideal vaccine profile because people don't like having to take needles, and for physicians, it's difficult to get the patient back for multiple doses," Catlin said. The genetically modified bacteria, live attenuated Salmonella typhi in the case of the Phase II study, is fermented, harvested and lyophylized (freeze dried). The lyophylized product is then reconstituted with water and combined with a buffer to neutralize acids, and is taken as a drink. The vaccine confers protection within a week of vaccination. The Phase II study will follow 180 healthy adult volunteers for six months and will compare two dosages - 1 x 108 colony forming units (cfu) and 1 x 109 cfu - and a placebo. Results are expected in the second quarter of next year.
