Immunogenicity, safety and immunological memory of a Brazilian meningococcal C conjugate vaccine on a phase II clinical trial

Introduction: Meningococcal disease (MD) is a public health burden. In many countries, including Brazil, serogroup C (MenC) is the main cause of MD, emphasizing the importance of continuous improvement of MenC conjugate vaccines. Methods: Phase II randomized, single-blinded study, with 360 healthy and meningococcal vaccine-naive children from 1 to 9 years of age: 240 received the candidate MenCC-Bio vaccine and 120 received the reference vaccine Neisvac-C®. The test vaccine was developed by Bio-Manguinhos∕Fiocruz and contained per dose: meningococcal C polysaccharide 10 μg (strain 2135) conjugated to tetanus toxoid (10–30 μg), and aluminum hydroxide (0.35 mg Al⁺³). Seroconversion (i.e., conversion to ≥1:8 or a 4-fold increase in serum bactericidal activity titers) and geometric mean titers (GMT) were evaluated. Adverse events were recorded for 30 days following vaccination. Duration of seroprotection was assessed 12 months after primary vaccination, and a booster dose was administered in children who had seroconverted initially. Results: Seroconversion rates were 226/240 (94.2 %; 95 % CI: 91.0 %; 96.4 %) for MenCC-Bio and 118/120 (98.3 %; 95 % CI: 94.1 %; 99.8 %) for Neisvac-C®. MenCC-Bio was considered non-inferior (difference in seroconversion −4.1 %; 95 % CI: −8.5 %; 0.3 %). However, post-vaccination bactericidal GMT was inferior (MenCC-Bio = 230; Reference vaccine = 1036), and test/reference GMT post-vaccination ratio was 0.22 (non-inferiority cutoff ≥0.6). Differences in immunogenicity were higher for children <5 years old. In the subset of children reassessed after 12 months, seroreversion for MenCC-Bio was 80.1 % and 46.0 % for the reference vaccine. Post-revaccination GMT was higher than after primary vaccination, and all seronegative volunteers became seropositive, indicating strong immunological memory. Both vaccines were well tolerated, and adverse events were mild or moderate. Conclusion: MenCC-Bio vaccine was equally safe but had lower immunogenicity compared to Neisvac-C®. Nevertheless, the high seroconversion rate and induction of immunological memory indicates its usefulness in Immunization Programs.