Safety and Immunogenicity of a <i>Klebsiella pneumoniae</i> Tetravalent Bioconjugate Vaccine (Kleb4V) Administered to Healthy Adults: A First-in-Human Phase I/II Randomized and Controlled Study

BACKGROUND: Safe and effective vaccines are urgently needed to prevent Klebsiella pneumoniae infections. We assessed safety and immunogenicity of a tetravalent bioconjugate vaccine Kleb4V, containing O antigen-polysaccharides of K. pneumoniae serotypes (O1v1, O2a, O2afg and O3b). METHODS: In this observer-blind, randomized, placebo-controlled, phase I/II trial (ClinicalTrials.gov NCT04959344), 166 healthy adults (16 aged 18-40 and 150 aged 55-70 years) were enrolled and randomized to receive 2 intramuscular injections of Kleb4V (16 or 64 μg of total O antigen with or without 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 doses. O1v1, O2a and O2afg specific IgG increased after the 1st vaccination and IgG 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. CONCLUSIONS: Kleb4V is the first K. pneumoniae conjugate vaccine candidate to reach clinical assessment. The Kleb4V bioconjugate was immunogenic and well tolerated in the target population of adults aged 55-70 years for the vaccine-serotypes.