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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Predicting vaccine effectiveness against invasive pneumococcal disease in children using immunogenicity data
Josiah Ryman1, Jessica Weaver2, Tianyan Hu3
1Quantitative Pharmacology and Pharmacometrics, Merck & Co., Inc, Rahway, NJ, USA.
Insights
New pneumococcal conjugate vaccines (PCVs) show reliable effectiveness predictions. Antibody levels from next-generation PCVs accurately estimate protection against shared serotypes, aiding vaccine development.
Area of Science:
- Immunology
- Vaccinology
- Public Health
Background:
- Antibody concentrations vary among pneumococcal conjugate vaccines (PCVs).
- Linking immunogenicity to vaccine effectiveness is crucial for next-generation vaccine assessment.
- Pneumococcal conjugate vaccines (PCVs) are vital for preventing invasive pneumococcal disease.
Purpose of the Study:
- To assess if antibody concentrations from next-generation PCVs can predict vaccine effectiveness.
- To establish a method for estimating protective antibody concentrations for pneumococcal serotypes.
- To validate predicted vaccine effectiveness against observed data.
Main Methods:
- Generated simulated reverse cumulative distribution curves using serotype-specific IgG concentrations.
- Combined IgG data with published vaccine effectiveness estimates for PCV7.
- Calculated protective antibody concentrations and predicted PCV13 effectiveness for shared serotypes.
Main Results:
- Predicted vaccine effectiveness for PCV13 closely matched observed effectiveness in the UK, Australia, and Germany.
- Median predicted effectiveness values were 93% vs. 90% (UK), 71% vs. 70% (Australia), and 91% vs. 90% (Germany).
- Demonstrated reliable estimation of vaccine effectiveness using IgG concentrations from next-generation PCVs.
Conclusions:
- Serotype-specific IgG concentrations from next-generation PCVs can reliably predict vaccine effectiveness.
- This method supports the evaluation of new pneumococcal conjugate vaccines.
- Immunogenicity data provides a valuable tool for estimating vaccine effectiveness against invasive pneumococcal disease.
Abstract:
The strength of the immune response, as measured by antibody concentrations, varies between pneumococcal conjugate vaccines (PCVs). Linking immunogenicity and effectiveness is necessary to assess whether changes in immune response from currently recommended PCVs to next-generation vaccines could impact effectiveness. Simulated reverse cumulative distribution curves were generated using published serotype-specific IgG concentrations with placebo or PCV7. This was combined with the published estimates of serotype-specific vaccine effectiveness of PCV7 against invasive pneumococcal disease to estimate the protective antibody concentration for each serotype in PCV7. Then, based on the published serotype-specific IgG concentrations in PCV13 recipients, reverse cumulative distribution curves were generated for the serotypes shared between PCV13 and PCV7. These estimated protective antibody concentration values were then used to predict the vaccine effectiveness of PCV13. The results were compared to published aggregate values for vaccine effectiveness. The aggregate median predicted vaccine effectiveness values were similar to previously reported observed values for the United Kingdom (93% versus 90%), Australia (71% versus 70%), and Germany (91% versus 90%). These results demonstrate that IgG concentrations of next-generation PCVs can be used to generate reliable estimates of vaccine effectiveness for serotypes shared with established PCVs.
