Reply to Pawaskar et al.

To the Editor— The commentary by Pawaskar et al. focused on the vaccine efficacy (VE) of the monovalent OKA/Merck vaccine. In our study, the 10-year GSK OKA/recombinant-immunotoxin (OKA/RIT) VE of 67.2% [1] was used, compared to Chan et al.’s 78.0% estimate [2] for the OKA/Merck vaccine. We wish to clarify why the 10-year OKA/Merck VE of 94.4% [3] was considered inappropriate, with emphasis on vaccination age, dose level (plaque-forming units [PFU]) and effectiveness studies.

The Kuter et al. [3] study was a 10-year follow-up of Weibel et al. [4], in which subjects aged 1–12 years (mean age, 4.43 years) received a 17,430 PFU-containing formulation. In the study by Povey et al. [1], children aged 12–22 months (mean age, 14.2 months) received the OKA/RIT vaccine with a potency of 1,995 PFU.

Studies by GSK and MSD suggest that older age at vaccination leads to a lower risk of varicella and a higher VE. Varis and Vesikari [5] demonstrated a lower VE with OKA/RIT vaccinees aged 10–18 months (64%) versus vaccinees aged 19–24 months (82%). Chan et al. [2] showed that at 5gp enzyme-linked immunosorbent assay, the risk of varicella infection decreased by ~ 80% in children aged 5.5 years versus children aged 1.5 years. Comparisons at equivalent titers indicated that the varicella infection risk decreased by ~ 73% in children aged 4.43 years versus children aged 14 months.

VE differences resulting from varying dose levels need to be highlighted as higher doses (10,000–17,000 PFU) are associated with better protection than lower doses (1,000 PFU) [5, 6]. This is illustrated by a crude comparison of the 100% OKA/Merck VE after 9 months of follow-up in Weibel et al. [4] with the 86% VE at 1 year in White et al. [7], in which the OKA/Merck dose ranged between 1,000 and 1,625 PFU among enrollees with a mean age of 3.98 years. Similarly, Kuter et al. [8], in a 7-year follow-up of Weibel et al. [4], with enrollees aged 4.7 years on average reported that 95% of vaccinees remained varicella-free following household exposure. This VE rate could be compared with Vessey et al.’s VE of 88.5% [9] over a 7-year period in enrollees with a median age of 3.6 years, with vaccine doses of 2,900–9,000 PFU and household exposure. The currently licensed monovalent OKA/Merck vaccine contains at least 1,350 PFU, which limits comparisons with prelicensure VE studies.

Overall, the bias risk with Kuter et al.’s VE in a comparative analysis with the OKA/RIT vaccine can be limited with Chan et al.’s VE estimate of 78.0% [2], for the reason previously reported, acknowledging limitations inherent to the absence of head-to-head efficacy studies across similar age groups and dose levels. A meta-analysis of observational studies by Marin et al. [10] reported a pooled 1-dose VE of 81% (95% confidence interval, 78%–84%) against any varicella with no differences by vaccine, in agreement with our conclusion on predicted similar effectiveness between GSK and MSD varicella-containing vaccines.

Conclusively, we believe that the most accurate VE estimate was used for the OKA/Merck vaccine. Importantly, both vaccines effectively reduce the varicella burden, with GSK varicella-containing vaccines potentially being more cost-effective.

Notes

Acknowledgments. The authors thank the Business & Decision Life Sciences platform for editorial assistance and letter coordination, on behalf of GSK. Maxime Bessieres (Business & Decision Life Sciences) coordinated the letter development and editorial support.

Financial support. GlaxoSmithKline Biologicals SA funded the study (HO-19-19880) and also funded the development and publication of this reply letter.

Potential conflicts of interest. E. I. H. A., M. H., and G. C. are employees of the GSK group of companies and hold shares in the GSK group of companies. O. C. is a consultant for Creativ-Ceutical on behalf of GSK and received fees for performing project-related tasks.

All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.