Safety, tolerability, and immunogenicity of a pentavalent meningococcal conjugate vaccine containing serogroups A, C, W-135, X, and Y in healthy adults: A randomized, single-center, active-controlled, double-blind, phase 1 study

Introduction Invasive meningococcal disease is a significant health threat, especially in sub-Saharan Africa, and it often results in outbreaks and severe epidemics. However, existing meningococcal vaccines lack protection against the emerging serogroup X, which has been on the rise since 2010. To address this gap, EuNmCV-5, a pentavalent meningococcal conjugate vaccine targeting serogroups A, C, W-135, X, and Y is newly developed. Methods A randomized, single-center, active-controlled, double-blind, first-in-human, phase 1 study was conducted in healthy Korean adults to evaluate the safety, tolerability, and immunogenicity of EuNmCV-5. The test drug, a pentavalent vaccine targeting serogroups A, C, W-135, X, and Y, was compared with the reference drug, a quadrivalent vaccine containing serogroups A, C, W-135, and Y. After obtaining written informed consent, sixty subjects were randomly assigned in a 1:1 ratio to receive a single intramuscular dose of either the test or reference drug. Safety assessment included monitoring anaphylactic reactions for 30 minutes, recording solicited adverse events for 7 days post-vaccination, unsolicited adverse events for 28 days post-vaccination, and serious adverse events over 180 days. Blood samples were collected before vaccination and 28 days after vaccination for immunogenicity assessment using a rabbit complement-dependent serum bactericidal antibody (rSBA) assay. Immunogenicity parameters, including seroconversion, seroprotection rates, geometric mean titers (GMT), and GMT ratio were compared between the two drugs. Result A total of sixty subjects completed the study as planned, and none of them reported anaphylactic reactions or life-threatening adverse events. The incidence rate and severity of adverse events were comparable between the test and reference drug. Following a single vaccination, the test drug induced seroconversion in over 85% of subjects and achieved a seroprotection rate exceeding 96.7% for all the targeted serogroups. The test drug showed higher seroconversion rates against serogroups A and C than the reference drug ( p  = 0.0016 and 0.0237, respectively) and maintained seroconversion rates greater than 90% for serogroups W-135 and Y. The GMT ratios (test to the reference drug) with corresponding 95% confidence intervals were 5.5 (2.3–13.2), 9.0 (2.5–32.4), 6.1 (2.2–16.7), 397.1 (161.8-974.4), and 5.0 (2.1–12.0) for serogroup A, C, W-135, X, and Y, respectively. Conclusion A single dose of EuNmCV-5 was safe and well-tolerated in healthy Korean adults. It elicited high seroconversion and seroprotection rates, along with a substantial increase in GMT for all targeted serogroups. ClinicalTrials.gov identifier : NCT05739292