# Immunogenicity and Safety of the ExPEC9V Escherichia coli Vaccine Co-Administered with a High-Dose Influenza Vaccine in Older Adults: A Placebo-Controlled, Randomized, Phase 3 Study

## TL;DR

This study tested a new E. coli vaccine given with a high-dose flu shot in older adults and found it was safe but immune responses to the E. coli vaccine were weaker when given together.

## Contribution

The study is the first Phase 3 trial evaluating co-administration of ExPEC9V and HD influenza vaccine in older adults.

## Key findings

- Co-administration met non-inferiority criteria for influenza immune responses but not for E. coli antigens.
- ExPEC9V was safe and well tolerated with no serious adverse events.
- Reactogenicity was higher with co-administration compared to separate administration.

## Abstract

Background: ExPEC9V is a 9-valent vaccine candidate designed to prevent invasive Escherichia coli disease, a life-threatening condition occurring when extraintestinal pathogenic E. coli (ExPEC) invade sterile sites. We evaluated immunogenicity and safety when ExPEC9V was co-administered with high-dose (HD) quadrivalent seasonal influenza vaccine. Methods: This Phase 3, double-blind, placebo-controlled study (NCT06134804) randomized 959 adults (≥65 years) to receive co-administration of ExPEC9V and HD quadrivalent seasonal influenza vaccine (CoAd) or each vaccine alone, 29 days apart (Control). Co-primary objectives were non-inferiority of co-administration versus separate administration following predefined criteria based on influenza strain-specific hemagglutination inhibition (HAI) antibody titers and ExPEC9V O-serotype binding antibody levels (multiplex electrochemiluminescence-based immunoassay), 29 days post vaccination. Reactogenicity and safety were assessed. Results: Co-administration of ExPEC9V with HD influenza vaccine demonstrated non-inferiority (upper bound of 2-sided 95% confidence interval [CI] < 1.5 for HAI geometric mean ratio [Control/CoAd]) for all influenza strains. Non-inferiority for ExPEC9V O-serotype antibody levels was not demonstrated (upper bound 95% CI > 1.5). One of nine serotypes met the non-inferiority criterion; eight did not, with four narrowly failing to meet the non-inferiority criterion. ExPEC9V immunogenicity was similar regardless of urinary tract infection history. ExPEC9V was safe and well tolerated, with no serious adverse events related to ExPEC9V. Reactogenicity rate was higher with co-administration. Conclusions: Co-administration of ExPEC9V with HD influenza vaccine met non-inferiority criteria of humoral immune responses for influenza antigens, but not for ExPEC9V O-serotype antigens. ExPEC9V, administered alone or with HD influenza vaccine, was safe and well tolerated, with an acceptable reactogenicity profile.