Safety and immunogenicity of a Klebsiella pneumoniae tetravalent bioconjugate vaccine (Kleb4V) administered to healthy adults: A first time in human phase I/II randomised and controlled study

BACKGROUND: Safe and effective vaccines are urgently needed to prevent infections caused by Klebsiella pneumoniae (K. pneumoniae), one of the most common antibiotic-resistant pathogens. We aimed to assess the safety and immunogenicity of a tetravalent bioconjugate vaccine Kleb4V, containing O antigen-polysaccharides of the most predominant K. pneumoniae serotypes (O1v1, O2a, O2afg and O3b). METHODS: In this observer-blind, randomised, placebo-controlled, phase I/II trial [ClinicalTrials.gov (number NCT04959344)], 166 healthy adults (18-40y n=16, 55-70y n=150) were enrolled and randomised to receive two intramuscular injections of Kleb4V (16μg or 64μg of total O-antigen +/- adjuvant AS03) or placebo on days 1 and 57. While the primary outcome was safety, the secondary outcomes included vaccine antigen immunogenicity. RESULTS: Kleb4V was well tolerated, with most solicited and unsolicited AEs of mild to moderate intensity. Kleb4V was immunogenic for all four vaccine-serotypes at both antigen doses. O1v1, O2a and O2afg specific IgG increased two weeks after the 1st vaccination and the immune response persisted at six months after the second vaccination. For three of the four vaccine-serotypes, the AS03-adjuvanted formulations showed a superior immune response. O3b responses were reduced compared to the other vaccine antigens. DISCUSSION: Kleb4V is the first K. pneumoniae conjugate vaccine candidate to reach clinical assessment. The Kleb4V bioconjugate was immunogenic, well tolerated and with an acceptable safety profile in the target population of adults aged 55-70 years for all 4 vaccine-serotypes.