A dose ranging study of 2 different formulations of 15-valent pneumococcal conjugate vaccine (PCV15) in healthy infants

Abstract

Background: Two new formulations of an investigational 15-valent pneumococcal conjugate vaccine (PCV15-A and PCV15-B) were developed using 2 different protein-polysaccharide conjugation processes and evaluated in separate phase I/II studies (NCT02037984 [V114-004] and NCT02531373 [V114-005]) to assess optimal concentrations of pneumococcal polysaccharide (PnPs) and Aluminum Phosphate Adjuvant.

Methods: Various lots of PCV15-A and PCV15-B containing different concentrations of PnPs and/or adjuvant were compared to PCV13 in young adults and infants. Adults received single dose and infants received 4 doses at 2, 4, 6, and 12-15 months of age. Adverse events (AEs) were collected after each dose. Serotype-specific immunoglobulin G (IgG) concentrations and opsonophagocytic activity (OPA) were measured prior and 30 days postvaccination in adults, at 1 month postdose 3 (PD3), pre-dose4, and postdose 4 (PD4) in infants.

Results: Safety profiles were comparable across vaccination groups. At PD3, serotype-specific IgG GMCs were generally lower for either PCV15 formulation than PCV13 for most shared serotypes. PCV15 consistently elicited higher antibody responses to the 2 serotypes unique to the vaccine (22F and 33F) and serotype 3 for which PCV13 was shown to be ineffective. Except for serotypes 6A and 6B, no dose-response effect was observed with increasing concentrations of PnPs and/or adjuvant.

Conclusion: PCV15 is safe and induces IgG and OPA responses to all 15 serotypes in the vaccine. No significant differences in antibody responses were observed with increases in PnPs and/or Aluminum Phosphate Adjuvant.

Keywords: Pneumococcal conjugate vaccine; immunogenicity; safety.

Figures

Figure 1.

Subject Disposition in Study #1 (PCV15-Formulation A).

Figure 2.

Postdose 3 IgG GMCs Figure 1: Subject Disposition in Study #1 (PCV15-Formulation A) (Infant Per-Protocol Population). ● Lot 1 = 1x:1x composition (2 μg/dose polysaccharide: 125 μg/dose adjuvant; except 6B)● Lot 2 = 0.5x:2x composition (1 μg/dose polysaccharide: 250 μg/dose adjuvant; except 6B)● Lot 3 = 1x:2x composition (2 μg/dose polysaccharide: 250 μg/dose adjuvant; except 6B)● Lot 4 = 2x:2x composition (4 μg/dose polysaccharide: 250 μg/dose adjuvant; except 6B)● PCV13 = Prevnar 13● IgG=immunoglobulin G; GMC=geometric mean concentration; PCV pneumococcal polysaccharide vaccine

Figure 3.

Postdose 3 IgG Response Rates in Study #1 (PCV15-Formulation A) (Infant Per-Protocol Population). ● Lot 1 = 1x:1x composition (2 μg/dose polysaccharide: 125 μg/dose adjuvant; except 6B)● Lot 2 = 0.5x:2x composition (1 μg/dose polysaccharide: 250 μg/dose adjuvant; except 6B)● Lot 3 = 1x:2x composition (2 μg/dose polysaccharide: 250 μg/dose adjuvant; except 6B)● Lot 4 = 2x:2x composition (4 μg/dose polysaccharide: 250 μg/dose adjuvant; except 6B)● PCV13 = Prevnar 13● IgG=immunoglobulin G; GMC=geometric mean concentration; PCV pneumococcal polysaccharide vaccine

Figure 4.

Subject Disposition in Study #2 (PCV15-Formulation B).

Figure 5.

Postdose 3 IgG GMCs in Study #2 (PCV15-Formulation B) (Infant Per-Protocol Population). ● Lot 5 = 1x:1x composition (2 μg/dose polysaccharide: 125 μg/dose adjuvant; except 6B)● Lot 6 = 2x:2x composition (4 μg/dose polysaccharide: 250 μg/dose adjuvant; except 6B)● PCV13 = Prevnar 13● IgG=immunoglobulin G; GMC=geometric mean concentration; PCV pneumococcal polysaccharide vaccine

Figure 6.

Postdose 3 IgG Response Rates in Study #2 (PCV15-Formulation B) (Infant Per-Protocol Population). ● Lot 5 = 1x:1x composition (2 μg/dose polysaccharide: 125 μg/dose adjuvant; except 6B)● Lot 6 = 2x:2x composition (4 μg/dose polysaccharide: 250 μg/dose adjuvant; except 6B)● PCV13 = Prevnar 13● IgG=immunoglobulin G; GMC=geometric mean concentration; PCV pneumococcal polysaccharide vaccine