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

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
• cc11/cc334 clonal complexes
• outbreak
• MenACWY-CRM conjugate vaccine
• MenC-CRM conjugate vaccine

Acknowledgments

The authors thank the children from whom sera were collected and their parents, as well as investigators and nurses involved in the original clinical trials. The authors are grateful to Frans Corthals (GSK, science writing), Lucia Fontana & Daniela Proietti (GSK, pre-clinical team) for their contribution to this post-hoc analysis. The authors thank the Modis and Business & Decision Life Sciences platforms for editorial assistance, manuscript coordination and writing support, on behalf of GSK. Petronela M. Petrar (Modis, on behalf of GSK) provided medical writing assistance and Bruno Dumont (Business & Decision Life Sciences, on behalf of GSK) coordinated manuscript development and editorial support.

Author’s contribution

All authors participated in the design or implementation or analysis and interpretation of the study; and the development of this manuscript. All authors had full access to the data and gave final approval before submission.

Disclosure of potential conflicts of interest

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.

Data availability statement

The product that is studied in this clinical study, together with the rights to the data and results generated, have been transferred to GSK by Novartis. The results summary for these studies (NCT00667602 and its extension NCT01345721) are available on the Novartis Clinical Trials Results website and can be accessed at https://www.novctrd.com/. For interventional studies that evaluate GSK medicines, anonymized patient-level data are made available to independent researchers, subject to review by an independent panel, at www.clinicalstudydatarequest.com within six months of publication. To protect the privacy of patients and individuals involved in our studies, GSK does not publicly disclose patient level data. Patient-level data for this study will be made available on www.clinicalstudydatarequest.com upon request, subject to any pre-existing rights and obligations and/or consents required under the relevant agreements governing or related to these studies.

Trademark statement

Menveo and Menjugate are trademarks owned or licensed by the GSK group of companies.

Additional information

Funding

GlaxoSmithKline Biologicals SA funded this research and was involved in all stages of study conduct, including analysis of the data. GlaxoSmithKline Biologicals SA also took in charge all costs associated with the development and publication of this manuscript.