Bactericidal antibodies against hypervirulent Neisseria meningitidis C field strains following MenC-CRM or MenACWY-CRM priming and MenACWY-CRM booster in children

Marzia Monica Giuliani, Alessia Biolchi, Pavitra Keshavan, Maria Moriondo, Sara Tomei, Laura Santini, Elena Mori, Alessandro Brozzi, Margherita Bodini, Francesco Nieddu, Silvia Ricci, Thembile Mzolo, Marco Costantini, Chiara Azzari, Michele Pellegrini, Marzia Monica Giuliani, Alessia Biolchi, Pavitra Keshavan, Maria Moriondo, Sara Tomei, Laura Santini, Elena Mori, Alessandro Brozzi, Margherita Bodini, Francesco Nieddu, Silvia Ricci, Thembile Mzolo, Marco Costantini, Chiara Azzari, Michele Pellegrini

Abstract

An increase in invasive meningococcal disease (IMD) incidence was observed in Tuscany in 2015/2016, mainly due to hypervirulent clonal complex (cc) 11 strains. In a post-hoc analysis, we assessed bactericidal activity of antibodies in sera from children primed with MenACWY-CRM or MenC-CRM conjugate vaccines and receiving a MenACWY-CRM booster dose against 5 meningococcal C (MenC) strains isolated from IMD cases. Sera collected from 90 infants/toddlers who participated in a phase III, open-label study (NCT00667602) and its extension (NCT01345721) were tested by serum bactericidal activity assay with human complement (hSBA). Children were primed with either MenACWY-CRM at 6-8 and 12 months of age (group 2_MenACWY; N = 30), MenACWY-CRM (group 1_MenACWY; N = 30), or MenC-CRM at 12 months of age (group 1_MenC; N = 30); all received MenACWY-CRM booster dose at 22-45 months of age. Four tested strains (FI001-FI004) were C:P1.5-1,10-8:F3-6:ST-11 (cc11) and 1 (FI005) was C:P1.7-4,14-6:F3-9:ST-1031 (cc334). Overall, immune responses tended to be higher against Fl002-FI004 than Fl001 and Fl005. Geometric mean titers were high in group 2_MenACWY (range: 94.8 [FI005]-588.1 [FI004]) and very high post-boosting with MenACWY-CRM in all groups (176.9 [FI005]-3911.0 [FI004]). Seroresponse rates tended to be higher in group 1_MenC (33.3% [FI005]-93.3% [FI004]) than in group 1_MenACWY (16.7% [FI005]-73.3% [FI004]). Irrespective of strains tested or the identity/number of priming doses, ≥96.7% of children had hSBA titers ≥1:8 post-MenACWY-CRM booster dose. MenACWY-CRM and MenC-CRM elicited bactericidal antibodies and immunological memory against hypervirulent cc11 and cc334 MenC strains responsible for IMD outbreaks.

Keywords: Hypervirulent MenC strains; MenACWY-CRM conjugate vaccine; MenC-CRM conjugate vaccine; cc11/cc334 clonal complexes; outbreak.

Conflict of interest statement

MMG, AB, PK, ST, LS, EM, AB, MB, TM, MC, and MP are employees of the GSK group of companies. MMG, PK and MP also hold shares in the GSK group of companies. At the time the analysis was conducted, MB was an employee of Randstad Italia SPA, working as a contractor for GSK. MM, FN, SR, and CA declare no financial conflicts of interest. All authors declare no non-financial conflict of interest.

Figures

Figure 1.
Figure 1.
Study design for parent and extension studies
Figure 2.
Figure 2.
Core genome analysis of the hypervirulent MenC strains
Figure 3.
Figure 3.
hSBA geometric mean titers (A) and geometric mean ratios (B) for hypervirulent MenC strains
Figure 4.
Figure 4.
Percentages of children with seroresponse against hypervirulent MenC strains
Figure A1.
Figure A1.
Percentages of children with hSBA titers ≥1:4 or ≥1:8 against the MenC vaccine reference strain (all time points)

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