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

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.

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).