Association Between Pre-Existing Anti-Diphtheria Toxoid IgG and Immune Responses to a CRM₁₉₇-Conjugated 14-Valent Pneumococcal Conjugate Vaccine in Infants: A Post Hoc Analysis of a Multicenter Phase III Trial

@article{thuluva2026association,
  title = {{Association Between Pre-Existing Anti-Diphtheria Toxoid IgG and Immune Responses to a CRM₁₉₇-Conjugated 14-Valent Pneumococcal Conjugate Vaccine in Infants: A Post Hoc Analysis of a Multicenter Phase III Trial}},
  author = {Subhash Thuluva and Subbareddy Gunneri and Siddalingaiah Ningaiah and Vijay Yerroju and Rammohan Reddy Mogulla and Kamal Thammireddy and Shivani Desai and Venkatalakshmi Gundu and Atul Jindal and Pradeep Nanjappa and Bheemisetty S. Chakravarthy and Niranjana S. Mahantashetti and Savita Verma and Manish Narang and Jog Pramod Prabhakar},
  journal = {Vaccines},
  year = {2026},
  month = sep,
  doi = {10.3390/vaccines14100854},
  url = {https://doi.org/10.3390/vaccines14100854},
  note = {CC BY},
}

TY  - JOUR
TI  - Association Between Pre-Existing Anti-Diphtheria Toxoid IgG and Immune Responses to a CRM₁₉₇-Conjugated 14-Valent Pneumococcal Conjugate Vaccine in Infants: A Post Hoc Analysis of a Multicenter Phase III Trial
AU  - Subhash Thuluva
AU  - Subbareddy Gunneri
AU  - Siddalingaiah Ningaiah
AU  - Vijay Yerroju
AU  - Rammohan Reddy Mogulla
AU  - Kamal Thammireddy
AU  - Shivani Desai
AU  - Venkatalakshmi Gundu
AU  - Atul Jindal
AU  - Pradeep Nanjappa
AU  - Bheemisetty S. Chakravarthy
AU  - Niranjana S. Mahantashetti
AU  - Savita Verma
AU  - Manish Narang
AU  - Jog Pramod Prabhakar
PY  - 2026
DA  - 2026/09/01
JO  - Vaccines
DO  - 10.3390/vaccines14100854
UR  - https://doi.org/10.3390/vaccines14100854
AB  - Background/Objectives: Maternally transferred antibodies protect infants early in life, but high concentrations can reduce immune responses to primary vaccination. CRM₁₉₇ is a nontoxic mutant of diphtheria toxin that retains antigenic similarity to the native protein. We therefore investigated whether anti-diphtheria antibodies present before vaccination were related to responses against pneumococcal polysaccharides conjugated to CRM₁₉₇. Methods: This post hoc analysis used data from a multicenter, randomized, single-blind phase III trial in which Indian infants received BE-PCV14/PNEUBEVAX 14® at 6–8, 10–12, and 14–16 weeks of age (commonly referred to as 6–10–14 weeks). Baseline anti-diphtheria toxoid IgG concentrations measured at 6–8 weeks were assessed in relation to serotype-specific pneumococcal IgG responses 28 days after dose 3. We evaluated these associations using categorical and continuous analyses with false-discovery-rate correction for serotype-specific comparisons. Results: Baseline and post-primary results were available for 603 of 650 infants in the co-administration cohort. Post-primary pneumococcal IgG concentrations did not differ significantly across the baseline anti-diphtheria IgG categories. Individual fold rises differed nominally among baseline anti-diphtheria IgG categories for serotype 5, but the difference did not remain significant after multiplicity correction. In the adjusted continuous models, geometric mean ratios (GMRs) associated with each 2-fold increase in baseline anti-diphtheria IgG ranged from 0.978 to 1.011, with no statistically significant associations after false-discovery-rate correction. Analyses stratified by baseline pneumococcal IgG similarly showed no consistent evidence of reduced responses. Conclusions: In this cohort, pre-existing anti-diphtheria toxoid IgG measured before vaccination, which was likely maternally derived, was not associated with a consistent reduction in post-primary serotype-specific pneumococcal IgG responses to CRM₁₉₇-conjugated BE-PCV14.
SN  - 2076-393X
ER  -