This is a Phase 2, double-blind (neither the researchers nor the participants know what treatment the participant is receiving), randomized (study medication assigned to participants by chance), placebo-controlled (an inactive substance; a pretend treatment [with no drug in it] that is compared in a clinical trial with a drug to test if the drug has a real effect), parallel group, multicenter (when more than one hospital work on a medical research study) study, with a single-blind, long-term follow-up to Year 3. The study will be split into 2 phases, a double-blind phase with screening (Day -12 to Day 1), Vaccination (Day 1) and Safety and Immunogenicity Follow-up (Day 1 up to Day 360), and a single-blind long-term follow-up phase thereafter until Year 3 for participants in placebo and two ExPEC4V dose groups selected based on the primary (Day 30) analysis. Participants will be stratified in 2 age groups (>=18 to less than [<] 50 years and >=50 years) and in each dosing group in each stratum randomized to a single vaccination with 1 of 5 doses of ExPEC4V or placebo. The duration of the double-blind phase (from randomization/vaccination) will be approximately 360 days for placebo participants and participants in the dose group selected based on the primary analysis, and approximately 180 days for the participants in the other groups. The duration of the single-blind long-term follow-up phase will be approximately 2 years after the double-blind phase for placebo participants and participants in the selected dose group. Participants' safety will be monitored throughout the study.