meCS6 + LT(R192G)

meCS6 + LT(R192G) is an experimental vaccine combination being developed against enterotoxigenic Escherichia coli (ETEC). This combination consists of microencapsulated colonization factor 6 antigen (meCS6) and a mutant form of heat-labile enterotoxin called LT(R192G) that serves as a mucosal adjuvant[1][2]. ## Composition and Mechanism The vaccine contains two main components: 1. **meCS6 (microencapsulated CS6)**: This is the colonization factor 6 antigen from ETEC that has been encapsulated in biodegradable poly(dl-lactide-co-glycolide) (PLG) microspheres to improve antigen delivery and uptake at mucosal inductive sites[1][4]. 2. **LT(R192G)**: This is a mutant form of the heat-labile enterotoxin (LT) from E. coli with a single amino acid substitution at position 192 (arginine to glycine). This mutation retains the immunogenicity and adjuvant properties of native LT while greatly reducing its toxicity[1][3]. ## Clinical Testing The combination has been evaluated in clinical trials for safety and immunogenicity: - In human trials, the vaccine was administered in different regimens (three-dose, 2-week interval or four-dose, 2-day interval)[2]. - Typical dosing included 1 mg of meCS6 with or without 2 μg of LT(R192G)[2][4]. - The vaccine was generally well-tolerated with no serious adverse events reported[2]. - One episode of diarrhea occurred in 1 of 30 subjects, which was consistent with LT(R192G)-related enterotoxicity in the four-dose adjuvanted group[1]. ## Immune Response - Serologic response to CS6 was relatively low in all regimens (0 to 27%)[2]. - CS6-IgA antibody-secreting cell (ASC) responses ranged from 36 to 86%, with the highest level in the three-dose adjuvanted regimen[2]. - As expected, serologic and ASC LT responses were limited to adjuvanted regimens[2]. ## Preclinical Testing The combination was also tested in non-human primates (Aotus nancymae): - Animals were given meCS6 (200 or 1000 μg) with or without 2 μg LT(R192G) in three doses at 2-week intervals[4]. - A dose-related serologic response to CS6 was observed, with higher responses at the 1000 μg dose[4]. - Safety parameters remained unchanged from baseline following all vaccinations[4]. The researchers concluded that further modifications to the delivery strategy and optimization of CS6 and adjuvant doses would be needed before conducting additional clinical trials with this ETEC vaccine candidate[2].