To the Editorial Board,
We read with interest the recent article by Mungall et al., entitled ‘A systematic review of invasive pneumococcal disease vaccine failures and breakthrough with higher-valency pneumococcal conjugate vaccines in children.’ [Citation1] With the potential for loss of immunogenicity with higher valency pneumococcal conjugate vaccines, it is important to characterize the risk of breakthrough disease and vaccine failures in children. The manuscript contributes to our understanding of this topic; however, we noted an important inaccuracy related to the newly approved 15-valent pneumococcal conjugate vaccine in the expert opinion section. Specifically, the author states: ‘Consistently, the 15-valent PCV failed non-inferiority versus PCV13 for three serotypes in terms of the percentage of responders and for up to five serotypes (for a non-adjuvanted formulation) in terms of geometric mean concentration ratios’ and cites results from a phase 2 clinical trial [Citation2].
The aforementioned reference summarizes results from an early phase 2 clinical trial evaluating different formulations of PCV15 (Protocol-003). Protocol-003 evaluated a 4-dose series of adjuvanted and nonadjuvanted formulations of V114 in infants, with PCV13 as the comparator. Based upon those results, the adjuvanted formulation was optimized and subsequently evaluated in the large Proof of Concept, phase 2 clinical trial in infants (Protocol-008). The results of this study demonstrated noninferiority for all 13 shared serotypes when comparing the 15-valent vaccine to PCV13, and were published in August 2020; thus they were available at the time the Mungall paper was submitted and under review [Citation3]. Results of the Proof of Concept trial informed the final vaccine formulation for the subsequent clinical development of V114 in infants, children, and adults; since then, Phase 3 study results have confirmed the findings of the Proof of Concept trial [Citation4]. Therefore, the formulations that were evaluated in the clinical trial cited by the author (Protocol-003) do not reflect the performance of the 15-valent pneumococcal conjugate vaccine that is now approved for use in the U.S [Citation5]. We request that this inaccuracy is promptly corrected.
Declaration of Interest
All authors are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may hold stock or stock options in Merck & Co., Inc., Rahway, NJ, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript.
Acknowledgments
We would like to thank Karyn Davis of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA for editorial assistance.
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References
- Mungall BA, Hoet B, Nieto Guevara J, et al. A systematic review of invasive pneumococcal disease vaccine failures and breakthrough with higher-valency pneumococcal conjugate vaccines in children. Expert Rev Vaccines. 2022;21(2):201–214.
- Greenberg D, Hoover PA, Vesikari T, et al. Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV15) in healthy infants. Vaccine. 2018;36(45):6883–6891.
- Platt HL, Greenberg D, Tapiero B, et al., V114-008 Study Group. A phase II trial of safety, tolerability and immunogenicity of V114, a 15-Valent pneumococcal conjugate vaccine, compared with 13-valent pneumococcal conjugate vaccine in healthy infants. Pediatr Infect Dis J. 2020 Aug;39(8):763–770. PMID: 32639460; PMCID: PMC7360095.
- Lupinacci R, Rupp R, Wittawatmongkol, et al. A phase 3, multicenter, randomized double-blind, active-comparator controlled study to evaluate the safety, tolerability, and immunogenicity of a 4-dose regimen of V114 in healthy infants (Pneu-PED). 12th World Congress of the World Society for Pediatric Infectious Diseases (Virtual). 2022 Feb 22 – 24. WSPID2022 Congress Abstracts Book: WSPID2022 Abstracts Book.
- Vaxneuvance. U.S. Food and Drug Administration (Silver Spring, MD: U.S. Food and Drug Administration). https://www.fda.gov/vaccines-blood-biologics/vaccines/vaxneuvance Accessed 22 July 2022