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
• safety
• immunogenicity

Author contributions

RR and DH: enrollment of subjects and/or data collection, review of the manuscript.

SG, JL, RDM, JH, LM: analysis and interpretation of data, and preparation of manuscript.

KN, RDM, JH, CA, MW, HP, PB, and LM: study concept and design, analysis and interpretation of data, and preparation of manuscript.

CA, MW, and HP: vaccine design and supply.

Disclosure of potential conflicts of interest

SG, JL, KN, RDM, JH, CA, MW, HP, PB, and LM are employees of the study sponsor.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ (sponsor). Although the sponsor formally reviewed a penultimate draft, the opinions expressed are those of the authors and may not necessarily reflect those of the sponsor. All co-authors approved the final version of the manuscript. The authors would like to acknowledge the assistance of Jon E. Stek and Daniel E. McCallus (both of Merck & Co., Inc., Kenilworth, NJ USA) for their editorial assistance.