A randomized, open-label study on the effect of nipocalimab on vaccine responses in healthy participants

Hum Vaccin Immunother. 2025 Dec;21(1):2491269. doi: 10.1080/21645515.2025.2491269. Epub 2025 Apr 15.

Abstract

Nipocalimab, a human immunoglobulin G (IgG) 1 monoclonal antibody, selectively binds the IgG-binding site on the neonatal Fc receptor (FcRn) and blocks IgG recycling, reducing IgG levels without impacting antigen presentation or T-/B-cell functions. In this phase 1, open-label study, we assessed the effect of nipocalimab on IgG response in healthy adults receiving T-cell-dependent/-independent vaccines (ie, tetanus toxoid [TT], diphtheria, and acellular pertussis vaccine [Tdap] and 23-polysaccharide pneumococcal vaccine [PPSV®23], respectively). Participants received either no drug (control) or intravenous nipocalimab (30 mg/kg at Week 0; 15 mg/kg at Weeks 2 and 4). All participants received Tdap and PPSV®23 vaccinations on Day 3 and were followed through Week 16. Twenty-nine participants completed the study (active, n=15; control, n=14). All participants mounted a response to Tdap vaccination, with 3 (20%) participants in the active arm and 7 (50%) participants in the control arm achieving a positive anti-TT response at Week 4 (primary endpoint; p=.089). Nipocalimab treatment was associated with numerically lower anti-TT and anti-pneumococcal (PCP)-specific IgG responses at Week 4 but comparable responses at Weeks 2 and 16. Overall, anti-TT IgG levels remained above the protective threshold (0.16 IU/mL) for all participants, and anti-PCP IgG levels remained above the 50 mg/L threshold and showed a 2-fold increase from baseline in both arms. Nipocalimab coadministration with Tdap and PPSV®23 was safe and well tolerated. Results suggest that nipocalimab does not impact the development of IgG responses to T-cell-dependent/-independent vaccines and participants treated with nipocalimab can follow recommended vaccination schedules.Trial registration number: NCT05827874.

Keywords: T cell–dependent; T cell–independent; immunoglobulin G; nipocalimab; vaccine.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Antibodies, Bacterial / blood
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Diphtheria-Tetanus-acellular Pertussis Vaccines* / administration & dosage
  • Diphtheria-Tetanus-acellular Pertussis Vaccines* / immunology
  • Female
  • Healthy Volunteers
  • Humans
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • Pneumococcal Vaccines* / administration & dosage
  • Pneumococcal Vaccines* / immunology
  • Tetanus Toxoid / administration & dosage
  • Tetanus Toxoid / immunology
  • Young Adult

Substances

  • Pneumococcal Vaccines
  • Immunoglobulin G
  • Antibodies, Bacterial
  • Antibodies, Monoclonal, Humanized
  • Diphtheria-Tetanus-acellular Pertussis Vaccines
  • 23-valent pneumococcal capsular polysaccharide vaccine
  • Tetanus Toxoid

Associated data

  • ClinicalTrials.gov/NCT05827874