Bioconjugate vaccine ExPEC4V (JNJ-63871860) was well-tolerated and elicited robust and functional antibody responses against Escherichia coli serotypes O1A, O2, O6A, and O25B at all doses and for all age groups, with durability of immune response for 1 year, according to a study published in The Lancet: Infectious Diseases.
ExPEC4V was developed to prevent invasive extra-intestinal pathogenic E coli (ExPEC) disease. This randomized, phase 2, placebo-controlled, double-blind study (NCT02546960) recruited healthy adults aged >18 years with body mass indexes of <35 kg/m² to assess the reactogenicity, safety, and immunogenicity of ExPEC4V. Participants (N=848) were randomly assigned to receive placebo or a single ExPEC4V dose (antigen O1A:O2:O6A:O25B content 4:4:4:4 μg [group 1]; 4:4:4:8 μg [group 2], 8:8:8:8 μg [group 3], 8:8:8:16 μg [group 4], or 16:16:16:16 μg [group 5]).
The primary study objectives were the assessment of the tolerability, safety, and immunogenicity of the vaccination and to determine the dose-dependent immunogenicity via enzyme-linked immunosorbent assay at 15 days postvaccination, in participants who had received at least 1 vaccination dose. Safety evaluation and antibody titers were used to select 2 doses of ExPEC4V for assessment up to day 360.
Of the 848 total participants, 99% (n=843) received placebo (n=86) or the ExPEC4V vaccine (n=757) and were included in the safety analysis. Of the 757 vaccinated participants. 29% (n=222) had a solicited local adverse event, and 43% (n=325) had a solicited systemic adverse event, compared with 35% (30 of 86) of control participants. Symptoms were mild to moderate, and the most frequent solicited local adverse event was tenderness or pain at injection site (205 [27.1%] of 757 in combined ExPEC4V groups) and the most frequent solicited systemic adverse event was fatigue (208 [27.6%] of 757). Only 2% of the total study cohort experienced a grade 3 event. At least 80% of participants had achieved a 2–fold or greater increase in serotype-specific IgG antibodies at day 15 (except O25B at the lowest dose, 103 [72%] of 144), and 66% (95% CI, 56.47-74.33) of participants in group 2 and 71% (62.13-78.95) in group 4 selected for long-term follow up maintained a 2 times or greater increase in serotype-specific antibody compared with baseline at day 360.
Researchers concluded, “All doses of the candidate ExPEC4V bioconjugated vaccine were well tolerated and elicited robust and functional antibody responses against each of the four vaccine serotypes. Two dosages (4:4:4:8 μg and 8:8:8:16 μg) showed durability of the immune response for 1 year.”
Study funding was provided by Janssen Pharmaceuticals.
Frenck RW Jr, Ervin J, Chu L, et al. Safety and immunogenicity of a vaccine for extra-intestinal pathogenic Escherichia coli (ESTELLA): a phase 2 randomised controlled trial [published online May 9, 2019]. Lancet Infect Dis. doi: 10.1016/S1473-3099(18)30803-X