Establishing a new human pneumococcal standard reference serum, MPRSS-01.

Area of Science:

• Immunology and Vaccinology
• Clinical Chemistry and Diagnostics

Background:

• Pneumococcal vaccine immunogenicity is assessed by measuring serotype-specific immunoglobulin G (IgG) antibody levels using the 007sp reference serum standard.
• The development of new pneumococcal conjugate vaccines (PCVs) with expanded serotype coverage necessitates a new reference serum standard.

Purpose of the Study:

• To establish a new pneumococcal reference serum standard (MPRSS-01) encompassing 33 serotypes, including novel ones not present in the existing 007sp standard.
• To ensure continuity and accuracy in measuring the immunogenicity of next-generation PCVs like V116.

Main Methods:

• Antibody concentrations for 33 pneumococcal serotypes were assigned in MPRSS-01 using the pneumococcal electrochemiluminescence assay.
• Direct calibration to 007sp was used for 24 established serotypes; cross-standardization with serotype 7F as a calibrator was employed for nine novel serotypes.
• Potential biases in cross-standardization were identified and addressed through adjustments, ensuring accurate IgG concentration assignments for novel serotypes.

Main Results:

• MPRSS-01 successfully assigned antibody concentrations for 33 pneumococcal serotypes, including nine novel ones.
• A robust method was established to link MPRSS-01 to the historical 007sp standard, enabling consistent immunogenicity assessments.
• The proposed methodology and assignments were accepted by the Center for Biologics Evaluation and Research (CBER).

Conclusions:

• The development of MPRSS-01 provides a crucial standard for evaluating the immunogenicity of advanced pneumococcal vaccines.
• This new standard bridges historical and contemporary pneumococcal reference sera, supporting the licensure of vaccines like V116.
• Accurate antibody concentration assignments are vital for ensuring the efficacy and safety of pneumococcal vaccines.