Use of Ensure® nutrition shakes as an alternative formulation method for live recombinant Attenuated Salmonella Typhi vaccines

Abstract

BackgroundTo be effective, orally administered live Salmonella vaccines must first survive their encounter with the low pH environment of the stomach. To enhance survival, an antacid is often given to neutralize the acidic environment of the stomach just prior to or concomitant with administration of the vaccine. One drawback of this approach, from the perspective of the clinical trial volunteer, is that the taste of a bicarbonate-based acid neutralization system can be unpleasant. Thus, we explored an alternative method that would be at least as effective as bicarbonate and with a potentially more acceptable taste. Because ingestion of protein can rapidly buffer stomach pH, we examined the possibility that the protein-rich Ensure® Nutrition shakes would be effective alternatives to bicarbonate.ResultsWe tested one Salmonella enterica serovar Typhimurium and three Salmonella Typhi vaccine strains and found that all strains survived equally well when incubated in either Ensure® or bicarbonate. In a low gastric pH mouse model, Ensure® worked as well or better than bicarbonate to enhance survival through the intestinal tract, although neither agent enhanced the survival of the S. Typhi test strain possessing a rpoS mutation.ConclusionsOur data show that a protein-rich drink such as Ensure® Nutrition shakes can serve as an alternative to bicarbonate for reducing gastric pH prior to administration of a live Salmonella vaccine.

Evaluating and optimizing oral formulations of live bacterial vaccines using a gastro-small intestine model

“…attenuated cholera strains Peru-15 [6] and CVD 103-HgR [7])a formulation that did not gain large scale adoption for Ty21a in spite of the greater immunogenicity of buffered liquid administration over capsules in clinical trials [8,9]. The poor palatability of bicarbonate buffers has led to the suggestion of alternate liquid formulations such as protein shakes [10] which provide effective protection of attenuated vaccine cells from gastric acid.…”

Salmonella Vaccines: Conduits for Protective Antigens

“…Moreover, induction of the acid-tolerance response induces expression of Salmonella SPI-1 and SPI-2 genes and facilitates increased invasion of the RASV into intestinal epithelial cells (96,(107)(108)(109). Regulated expression of the arginine and/or glutamate decarboxylase systems in S. Typhi RASVs, coupled with using Ensure to modulate the stomach pH (110), should facilitate successful immunization of humans (which have a lower stomach pH after fasting than do mice).…”