ExPEC vaccine candidate shows promise in phase 2 trial

An extra-intestinal pathogenic Escherichia coli (ExPEC) vaccine candidate was well tolerated and elicited robust and functional responses across all serotypes, doses, and age groups in a phase 2 trial, researchers from Janssen Pharmaceuticals reported yesterday in The Lancet Infectious Diseases.

The randomized, double-blind placebo-controlled trial, designed and funded by Janssen, involved 848 healthy adults who were randomly assigned to receive a single dose of one of five ExPEC4V formulations or placebo. ExPEC4V is a four-valent vaccine comprised of the E coli O1A, O2, O6A, and O25B antigens bioconjugated to the protein carrier Pseudomonas aeruginosa exoprotein A. The primary objectives were the evaluation of safety, tolerability, and immunogenicity of ExPEC4V and determination of its dose-dependent immunogenicity 15 days after vaccination in individuals who had received at least one dose. On the basis of day 15 immunogenicity and day 30 safety data, two ExPEC4V doses were selected for assessment up to day 360.

Overall, 843 participants were included in the safety analysis; of these, 757 received the vaccine and 86 received the placebo. Of 757 participants vaccinated with ExPEC4V, 222 (29%) had a solicited local adverse event and 325 (43%) had any solicited systemic adverse event, compared with 11 (13%) and 30 (35%) of 86 participants in the control group. Symptoms were mild-to-moderate. The most frequently reported solicited local adverse event was pain or tenderness (205 of 757 [27.1%] in combined ExPEC4V groups) and the most frequently reported solicited systemic adverse event was fatigue (208 of 757 [27.6%]). Only 13 of 843 (2%) had a grade 3 event.

At day 15, 80% or more of all participants achieved two times or greater increase in serotype-specific IgG antibodies (except O25B at the lowest dose, 103 of 144 [72%]). Durable serotype-specific antibody responses were observed in groups 2 and 4 up to day 360, with 65% or more in group 2 and 71% or more in group 4 maintaining two times or greater increase in IgG from baseline.

ExPEC is the most common Gram-negative bacterial pathogen in humans, causing diverse and serious invasive diseases across all age groups, including urinary tract infections (UTIs), bacteremia, neonatal meningitis, surgical site infections, abdominal and pelvic infections, and nosocomial pneumonia. The expansion of multidrug-resistant ExPEC clones, such as E coli sequence type 131, has contributed to increased treatment failure and mortality.