Safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in children with SCD: a V114-023 (PNEU-SICKLE) study

Abstract

Sickle cell disease (SCD) is an inherited red blood cell disease that results in a multitude of medical complications, including an increased risk of invasive disease caused by encapsulated bacteria, such as Streptococcus pneumoniae. Pneumococcal vaccines have contributed to a significant reduction in pneumococcal disease (PD) in children and adults, including those with SCD. This phase 3 study evaluated the safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), in children with SCD. A total of 103 children aged 5 to 17 years with SCD were randomized and received a single dose of V114 or Prevnar 13 (PCV13). Safety was evaluated as the proportion of participants with adverse events (AEs). Serotype-specific immunoglobulin G (IgG) levels and opsonophagocytic activity (OPA) were measured immediately before vaccination and 30 days after vaccination. Overall, the rates of injection-site and systemic AEs reported after vaccination were similar between the vaccination groups. Up to 6 months after vaccination, serious AEs were those expected for patients with SCD, and none were assessed to be vaccine related. IgG geometric mean concentrations (GMCs) and OPA geometric mean titers (GMTs) for the 13 shared serotypes were generally comparable between recipients of V114 and PCV13. Additionally, V114 induced immune responses to serotypes 22F and 33F, which are not included in PCV13. The safety and tolerability profiles of V114 were consistent with those reported for PCV13. Immune responses following vaccination with V114 were generally comparable to PCV13 for the shared serotypes and higher for unique serotypes 22F and 33F. These results support the use of V114 in children with SCD. This trial was registered at www.clinicaltrials.gov as #NCT03731182.

Conflict of interest statement

Conflict-of-interest disclosure: R.T.W., M.P., G.B., Q.S., K.F., R.M., G.T., R.L., and L.M. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, and may hold stock in Merck & Co, Inc, Rahway, NJ. K.B. was an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ at the time of the study, may hold stock in Merck & Co, Inc, Rahway, NJ, and is currently employed by Affinivax Inc. D.J. has received i) speaker honoraria from Pfizer, GlaxoSmithKline, Janssen, Sanofi, Abbott, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, ii) honoraria as a clinical trial investigator from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, iii) honoraria as a clinical trial investigator from GlaxoSmithKline, Takeda, and Janssen outside the submitted work, and iv) an institutional research grant from Pfizer outside the submitted work. R.D. reports grants or contracts from Pfizer, Medimmune, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ; consulting fees from Pfizer, Biondvax, MeMed, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ; serving on advisory boards of Pfizer, Biondvax, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ; providing expert testimony for Pfizer; and participating on an advisory board for Pfizer, Biondvax, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ. P.R. has served on vaccine advisory boards for Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, Pfizer, and GlaxoSmithKline, and received institutional grant funding from GlaxoSmithKline and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, outside the submitted work. The remaining authors declare no competing financial interests.

© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Graphical abstract

Figure 1.

Participant disposition. ∗One participant in the V114 group was randomized but not vaccinated because of the physician’s decision.

Figure 2.

Assessment of solicited AEs. The proportion of participants reporting solicited AEs within 14 days of vaccination is shown by the intensity. ∗For injection-site erythema, induration, and swelling, 0 to ≤1 in. was considered mild, >1 to ≤3 in. was considered moderate, and >3 in. was considered severe. V=V114, P=PCV13.

Figure 3.

Serotype-specific IgG GMCs at 30 days after vaccination. The serotype-specific IgG GMCs and 95% confidence intervals on day 30 are shown for each vaccination group.

Figure 4.

Serotype-specific OPA GMTs at 30 days after vaccination. The serotype-specific OPA GMTs and 95% confidence intervals on day 30 are shown for each vaccination group.