Safety and Immunogenicity of a 20-valent Pneumococcal Conjugate Vaccine in Healthy Infants in the United States

Shelly Senders, Nicola P Klein, Erik Lamberth, Allison Thompson, Jelena Drozd, James Trammel, Yahong Peng, Peter C Giardina, Kathrin U Jansen, William C Gruber, Daniel A Scott, Wendy Watson, Shelly Senders, Nicola P Klein, Erik Lamberth, Allison Thompson, Jelena Drozd, James Trammel, Yahong Peng, Peter C Giardina, Kathrin U Jansen, William C Gruber, Daniel A Scott, Wendy Watson

Abstract

Background: The development and widespread use of pneumococcal conjugate vaccines (PCVs) substantially reduced the global burden of pneumococcal disease. Expanding the serotypes covered by PCVs may further reduce disease burden. A 20-valent PCV (PCV20) has been developed to add coverage for 7 additional serotypes (8, 10A, 11A, 12F, 15B, 22F and 33F) to those in the existing 13-valent PCV (PCV13). This phase 2 study evaluated the safety, tolerability and immunogenicity of PCV20 in healthy US infants.

Methods: In this randomized, active-controlled, double-blind study, 460 infants were randomized 1:1 to receive a 4-dose series of either PCV20 or PCV13 at 2, 4, 6 and 12 months of age. Solicited local reactions and systemic events, adverse events (AEs) and serious AEs were recorded. Immunogenicity was assessed by measuring serotype-specific IgG concentrations and opsonophagocytic activity titers at 1 month after Dose 3, before Dose 4 and 1 month after Dose 4.

Results: Of 460 infants, 82.8% completed the 1-month visit after Dose 4. Local reactions and systemic events were mostly mild to moderate in severity and similar between the PCV20 and PCV13 groups. Treatment-related AEs were uncommon, with no related serious AEs or deaths reported. IgG and opsonophagocytic activity responses elicited by PCV20 were robust and demonstrated a booster response after Dose 4.

Conclusions: Administration of PCV20 in US infants was well tolerated, with a safety profile similar to PCV13, and induced robust serotype-specific immune responses. These findings support continued development of PCV20 in the pediatric population.

Trial registration: ClinicalTrials.gov NCT03512288.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

FIGURE 1.
FIGURE 1.
Percentages of participants with reported (A) local reactions and (B) systemic events after each dose. For Dose 1, PCV20, n = 229; PCV13, n = 224. For Dose 2, PCV20, n = 215; PCV13, n = 204. For Dose 3, PCV20, n = 201; PCV13, n = 204. For Dose 4, PCV20, n = 186; for PCV13, n = 185. n values refer to the number of participants with any electronic diary data reported after the specified dose. Severity was graded by the parents/legal guardians as instructed by the investigator staff (mild: Grade 1, moderate: Grade 2, severe: Grade 3). For redness and swelling, grading was based on size (mild, >0 to 2.0 cm; moderate, >2.0 to 7.0 cm; severe, >7 cm) or description of the affected area. For pain and all systemic events, grading was based on degree to which the event interfered with activity. Fever was reported as a range of temperatures (mild, ≥38.0–38.4°C; moderate, >38.4–38.9°C; severe, >38.9–40.0°C).

References

    1. Pilishvili T, Lexau C, Farley MM, et al. ; Active Bacterial Core Surveillance/Emerging Infections Program Network. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis. 2010;201:32–41.
    1. Wahl B, O’Brien KL, Greenbaum A, et al. . Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15. Lancet Glob Health. 2018;6:e744–e757.
    1. World Health Organization. Pneumococcal conjugate vaccines in infants and children under 5 years of age: WHO position paper - February 2019. 2019;94:85–104. Available at: . Accessed September 23, 2020.
    1. Geno KA, Gilbert GL, Song JY, et al. . Pneumococcal capsules and their types: past, present, and future. Clin Microbiol Rev. 2015;28:871–899.
    1. Centers for Disease Control and Prevention. Manual for the surveillance of vaccine-preventable diseases. Chapter 11: pneumococcal. 1996. Available at: . Accessed February 1, 2021.
    1. Pilishvili T, Gierke R, Farley MM, et al. . 1470. Epidemiology of invasive pneumococcal disease (IPD) following 18 years of pneumococcal conjugate vaccine (PCV) use in the United States. Open Forum Infectious Diseases. 2020;7:S736–S737.
    1. Moore MR, Link-Gelles R, Schaffner W, et al. . Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance. Lancet Infect Dis. 2015;15:301–309.
    1. Vadlamudi NK, Chen A, Marra F. Impact of the 13-valent pneumococcal conjugate vaccine among adults: a systematic review and meta-analysis. Clin Infect Dis. 2019;69:34–49.
    1. Wiese AD, Griffin MR, Grijalva CG. Impact of pneumococcal conjugate vaccines on hospitalizations for pneumonia in the United States. Expert Rev Vaccines. 2019;18:327–341.
    1. Marom T, Tan A, Wilkinson GS, et al. . Trends in otitis media-related health care use in the United States, 2001-2011. JAMA Pediatr. 2014;168:68–75.
    1. Fireman B, Black SB, Shinefield HR, et al. . Impact of the pneumococcal conjugate vaccine on otitis media. Pediatr Infect Dis J. 2003;22:10–16.
    1. Balsells E, Guillot L, Nair H, et al. . Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era: a systematic review and meta-analysis. PLoS One. 2017;12:e0177113.
    1. Hausdorff WP, Hanage WP. Interim results of an ecological experiment - conjugate vaccination against the pneumococcus and serotype replacement. Hum Vaccin Immunother. 2016;12:358–374.
    1. Kaplan SL, Barson WJ, Lin PL, et al. . 176. Selected impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on invasive pneumococcal disease (IPD) at eight children’s hospitals in the United States. 2014–2019. Open Forum Infect Dis. 2020;7(suppl 1):S216–S217.
    1. GBD 2016 Lower Respiratory Infections Collaborators. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet Infect Dis. 2018;18:1191–1210.
    1. Cohen R, Levy C, Ouldali N, et al. . Invasive disease potential of pneumococcal serotypes in children after PCV13 implementation. Clin Infect Dis. 2021;72:1453–1456.
    1. Tomczyk S, Lynfield R, Schaffner W, et al. . Prevention of antibiotic-nonsusceptible invasive pneumococcal disease with the 13-valent pneumococcal conjugate vaccine. Clin Infect Dis. 2016;62:1119–1125.
    1. Metcalf BJ, Gertz RE, Jr, Gladstone RA, et al. . Strain features and distributions in pneumococci from children with invasive disease before and after 13-valent conjugate vaccine implementation in the USA. Clin Microbiol Infect. 2016;22:e9–e29.
    1. Harboe ZB, Thomsen RW, Riis A, et al. . Pneumococcal serotypes and mortality following invasive pneumococcal disease: a population-based cohort study. PLoS Med. 2009;6:e1000081.
    1. Oligbu G, Collins S, Sheppard CL, et al. . Childhood deaths attributable to invasive pneumococcal disease in England and Wales, 2006-2014. Clin Infect Dis. 2017;65:308–314.
    1. Cui YA, Patel H, O’Neil WM, et al. . Pneumococcal serotype distribution: a snapshot of recent data in pediatric and adult populations around the world. Hum Vaccin Immunother. 2017;13:1–13.
    1. Pilishvili T, Gierke R, Farley M, et al. . Epidemiology of invasive pneumococcal disease (IPD) following 18 years of pneumococcal conjugate vaccine (PCV) use in the United States. Open Forum Infect Dis. 2020;7(suppl 1):S736–S737.
    1. Thompson A, Lamberth E, Severs J, et al. . Phase 1 trial of a 20-valent pneumococcal conjugate vaccine in healthy adults. Vaccine. 2019;37:6201–6207.
    1. Hurley D, Griffin C, Young M, et al. . Safety, tolerability, and immunogenicity of a 20-valent pneumococcal conjugate vaccine (PCV20) in adults 60 to 64 years of age [published online ahead of print July 27, 2020]. Clin Infect Dis. doi: 10.1093/cid/ciaa1045
    1. Pavliakova D, Giardina PC, Moghazeh S, et al. . Development and validation of 13-plex luminex-based assay for measuring human serum antibodies to Streptococcus pneumoniae capsular polysaccharides. mSphere. 2018;3:e00128–e00118.
    1. Tan CY, Immermann FW, Sebastian S, et al. . Evaluation of a validated luminex-based multiplex immunoassay for measuring immunoglobulin G antibodies in serum to pneumococcal capsular polysaccharides. mSphere. 2018;3:e00127–e00118.
    1. Perdrizet J, Wasserman M, Farkouh RA, et al. . Estimated pneumococcal disease and economic burden for current and future vaccine serotypes in United States in children under five years of age. In: International Symposium on Pneumococci and Pneumococcal Diseases. Digital Library; 2020.
    1. Perdrizet J, Chilson E, Wasserman M, et al. . Current and future pneumococcal conjugate vaccine serotype-specific burden in the United States adult population. In: International Symposium on Pneumococci and Pneumococcal Diseases. Digital Library; 2020.
    1. Pfizer Inc. Data from Pfizer’s adult and pediatric clinical trial programs for 20-valent pneumococcal conjugate vaccine presented at IDWeek 2020. 2020. Available at: . Accessed January 6, 2021.

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