(W-106) Comparing Predicted Serotype-specific Vaccine Effectiveness of Pneumococcal Conjugate Vaccines V114 and PCV20 in Children using a novel model-based meta-analysis approach

Maurice Ahsman, PharmD, PhD – Director, Quantitative Pharmacology and PMX, MSD Brazil; Jeffrey Sachs, ScB, ScM, PhD, ACDRS – Distinguished Scientist, Exec. Dir., Quantitative Pharmacology and PMX, Merck & Co., Inc., USA; Josiah Ryman, PharmD, PhD – Director, Former: Merck & Co., Inc., USA, Current: EMD Serono; Ka Lai Yee, PhD – Sr. Director, Quantitative Pharmacology and PMX, Merck & Co., Inc., USA; Natalie Banniettis, MD, FAAP – Sr. Prin. Scientist, Pneumococcal Vaccines Section, Clinical Research, Merck & Co., Inc., USA; Thomas Weiss, MPH, DrPH – Scientific Assoc. VP, PL Vaccines, Outcomes Research, Merck & Co., Inc., USA; Jessica Weaver, MPH, PhD – Prin. Scientist, PL Vaccines-Adult, Outcomes Research, Merck & Co., Inc., USA

Objectives: Invasive pneumococcal disease incidence in children has decreased substantially since the introduction of pneumococcal conjugate vaccines (PCVs) against the 7 (PCV7) and, later, 6 more (PCV13) serotypes (STs) clinically relevant in the US. In the absence of placebo-controlled vaccine efficacy trials, new PCVs are evaluated based on the vaccine-induced, serotype-specific (SS) immune response levels (immunoglobulin G titers, IgGs), as they have been demonstrated to predict efficacy. New PCVs are approved if induced SS IgGs are non-inferior to those of PCVs with demonstrated efficacy. SS IgGs can decrease with increased PCV valency, so predicting vaccine effectiveness (VE) of new PCVs can be critical to supporting public health decisions. This work predicts (from IgGs) SS VEs for the 13 serotypes shared between earlier and new PCVs.

Methods.The model-based meta-analysis combined real-world vaccine effectiveness (VE) data with IgG data from clinical trials. Reverse cumulative distribution curves (RCDCs) were simulated using SS IgGs observed in placebo, PCV7, and PCV13 recipients. These were combined with published SS VEs for PCV7 and PCV13 to derive the protective IgG “threshold” (“Cp”) for each of the 13 serotypes. SS IgGs from V114 and PCV20 recipients in clinical trials gave RCDCs for each of the 13 serotypes shared with PCV13. The RCDCs were combined with Cp values to predict, for V114 and PCV20, VEs for the 13 shared serotypes [1]. Post-primary series titers were used for predicting SS Cp and VE for both 2+1 and 3+1 dosing regimens (two or three infant doses, respectively, followed by a toddler dose). 2+1 predictions used V114 and PCV20 titers from clinical trials in EU, Russian, and Australian pediatric populations for which this regimen is routinely recommended; PCV13 VEs were from an EU pediatric population. 3+1 predictions used V114 and PCV20 titers from clinical trials in the US and Puerto Rico (where 3+1 is routinely recommended); PCV13 VEs were from a US pediatric population. Resampling the relevant distributions accounted for variability and uncertainty in the available data.

Results: Predicted SS VEs against PCV13 serotypes are higher for V114 than PCV20, for both 2+1 and 3+1 dosing regimens, particularly for the still-prevalent serotype ST 3 (93% and 98% for V114, 47% and 64% for PCV20, respectively, for 2+1 and 3+1 dosing regimens). A V114 2+1 regimen had predicted VEs comparable to those of PCV13 for the other 12 shared serotypes, with VE for a V114 3+1 regimen predicted to be lower (than PCV13) for ST 6A and higher for ST 19F. The predictive power of this framework and its consistency (with observed data) is re-enforced with a vachette [2] visualization of the results considering serotype and regimen as covariates.

Conclusions: The approach can provide informative VE predictions in the absence of placebo-controlled clinical trials, and vachette visualization can help understand the results across regimens and serotypes.

Citations: [1] J Ryman, J Weaver, T Hu, DM Weinberger, KL Yee, JR Sachs, Predicting vaccine effectiveness against invasive pneumococcal disease in children using immunogenicity data. npj Vaccines 7, 140 (2022). https://doi.org/10.1038/s41541-022-00538-1

J Ryman, J Weaver, KL Yee, JR Sachs, Predicting effectiveness of the V114 vaccine against invasive pneumococcal disease in children. Expert Review of Vaccines, 21(10) (2022). https://doi.org/10.1080/14760584.2022.2112179

J Ryman, JR Sachs, KL Yee, N Banniettis, J Weaver, T Weiss, Predicted serotype-specific effectiveness of pneumococcal conjugate vaccines V114 and PCV20 against invasive pneumococcal disease in children. Expert Review of Vaccines, 23(1) (2024) https://doi.org/10.1080/14760584.2023.2292773

J Ryman, JR Sachs, N Banniettis, T Weiss, M Ahsman, KL Yee, J Weaver. Potential serotype-specific effectiveness against IPD of pneumococcal conjugate vaccines V114 and PCV20 in children given a 2+1 dosing regimen. Expert Review of Vaccines, 23(1), (2024) https://doi.org/10.1080/14760584.2024.2335323

[2] https://certara.shinyapps.io/vachette/