Inci Yildirim, MD, PhD, MSc
Principal InvestigatorProfessor of Pediatrics (Infectious Disease) and of Epidemiology (Microbial Diseases)
Immune signatures of vaccine responses in children with sickle cell disease
Organizations
Principal Investigators
Description
Introduction
This project aims to identify molecular and immune signatures that underlie impaired vaccine responses in children with sickle cell disease by analyzing innate and adaptive immunity, as well as whole-genome transcriptional changes after vaccination. Using advanced single-cell and spatial profiling techniques, the research will generate detailed mechanistic insights to enhance vaccine effectiveness and reduce infection-related complications in this vulnerable group.
- Status
- Ongoing
- Timeline
- 12/01/2023 - 10/31/2028
- Last Updated
- 06/01/2026
- Project Contact
- Inci Yildirim
Overview
Children with sickle cell disease (SCD) face a significantly higher risk of severe infections due to both their underlying condition and impaired responses to routine vaccinations. Although vaccines are essential for protecting this vulnerable population, many children with SCD fail to develop adequate immunity, and the mechanisms responsible for these poor responses remain unclear. There is a critical need to understand how chronic inflammation and immune system dysregulation in SCD alter both innate and adaptive immune pathways following vaccination.
This project seeks to uncover the molecular and immune characteristics that distinguish vaccine responses in children with SCD, using advanced single-cell and spatial profiling to analyze changes in immune function and gene expression. By mapping these immune signatures, the research aims to provide detailed mechanistic insights that could guide the development of targeted strategies to enhance vaccine efficacy. Ultimately, this work has the potential to inform new interventions that reduce infection-related complications and improve health outcomes for children with SCD and other high-risk groups.
Themes
Techniques
Collaborators
Leadership
Research Team
Name | Title | Institution |
|---|---|---|
Albert C Shaw, MD, PhD | Co-Principal Investigator | Yale School of Medicine |
Outcomes
Publications
Invasive Pneumococcal Disease After 2 Decades of Pneumococcal Conjugate Vaccine Use.
Yildirim I, Lapidot R, Shaik-Dasthagirisaheb Y, Hinderstein S, Lee H, Klevens M, Grant L, Arguedas Mohs A, Cane A, Madoff L, Johnson H, Ivanof C, Burns M, Pelton S. Invasive Pneumococcal Disease After 2 Decades of Pneumococcal Conjugate Vaccine Use. 2023, 153 PMID: 38087952, DOI: 10.1542/peds.2023-063039.Peer-Reviewed Original ResearchConceptsInvasive pneumococcal diseaseIPD casesPCV13 eraPneumococcal diseaseCases of IPDIncidence of IPDRates of IPDPneumococcal conjugate vaccine useSerotype 15B/CImplementation of PCV13Non-PCV13 serotypesPneumococcal conjugate vaccineConfidence intervalsStatewide surveillance systemIPD incidence ratesIPD ratesPenicillin nonsusceptibilityConjugate vaccineVaccine serotypesSerotype 19ASterile sitesIncidence rateVaccine useLower incidenceVaccine formulationsA comprehensive analysis of serotype-specific invasive capacity, clinical presentations, and mortality trends of invasive pneumococcal disease
Yildirim M, Keskinocak P, Hinderstein S, Tran K, Dasthagirisaheb Y, Madoff L, Pelton S, Yildirim I. A comprehensive analysis of serotype-specific invasive capacity, clinical presentations, and mortality trends of invasive pneumococcal disease. Vaccine 2025, 47: 126692. PMID: 39778476, PMCID: PMC12859698, DOI: 10.1016/j.vaccine.2024.126692.Peer-Reviewed Original ResearchConceptsInvasive pneumococcal diseasePneumococcal conjugate vaccineClinical presentationInvasive diseasePneumococcal diseaseAnnual incidence of invasive pneumococcal diseaseIncidence of invasive pneumococcal diseaseInvasive capacityInvasive pneumococcal disease serotypesPost-PCV13 eraReduced invasive diseasePneumococcal nasopharyngeal colonizationYears of ageNP carriageSerotype 35BPost-PCV13Respiratory seasonsCarriage prevalenceNasopharyngeal colonizationStreptococcus pneumoniaeConjugate vaccineSerotype 18CAnnual incidenceVaccination strategiesNP isolatesSerotype specific pneumococcal vaccine effectiveness in children with sickle cell disease: A two-decade analysis
Zhang Z, Yildirim M, Keskinocak P, Dasthagirisaheb Y, Hinderstein S, Tran K, Crockett M, Burns M, Johnson H, Popstefanija M, Madoff L, Pelton S, Yildirim I. Serotype specific pneumococcal vaccine effectiveness in children with sickle cell disease: A two-decade analysis. Vaccine 2025, 56: 127193. PMID: 40318350, PMCID: PMC12859699, DOI: 10.1016/j.vaccine.2025.127193.Peer-Reviewed Original ResearchIncidence rate ratiosInvasive pneumococcal diseaseSickle cell diseaseIncidence ratePost-PCV13 periodCalculated incidence ratesValency vaccinesVaccine effectivenessPneumococcal diseaseHealthy childrenRates of invasive pneumococcal diseasePopulation-basedCell diseaseHealth conditionsRate ratiosNon-PCV13 serotypesPneumococcal vaccine effectivenessVulnerable populationsBootstrapping resamplingIncreased riskHigher IRNon-PCV13Genetic hematological diseasesHematological diseasesVaccine formulationsClinical Features and Outcomes of Pneumococcal Bacteremia in Children With Sickle Cell Disease in the Pneumococcal Conjugate Vaccine Era
Yee M, Abel L, Kalmus G, Patel A, Elmontser M, Bakshi N, Wang Y, Gonzalez M, Adamkiewicz T, Yildirim I, Lane P. Clinical Features and Outcomes of Pneumococcal Bacteremia in Children With Sickle Cell Disease in the Pneumococcal Conjugate Vaccine Era. Pediatric Blood & Cancer 2025, 72: e31881-e31881. PMID: 40563215, PMCID: PMC12699443, DOI: 10.1002/pbc.31881.Peer-Reviewed Original ResearchConceptsSickle cell diseasePneumococcal bacteremiaInstitutional cohortClinical featuresMedian time to culture positivityInstitutional cohort of childrenOutcome of pneumococcal bacteremiaRisk of pneumococcal bacteremiaTime to culture positivityCell diseasePneumococcal conjugate vaccine eraProgression to severe diseaseAcute chest syndromeLong-term sequelaeCohort of childrenPenicillin nonsusceptibilityPPSV23 serotypesChest syndromeHearing lossPenicillin prophylaxisInvasive infectionsEmpirical treatmentNeurocognitive defectsProphylactic penicillinSerotype informationUnravelling the Immunological Enigma of Sickle Cell Disease: Current Understanding and Future Directions
Jamwal S, Calhoun C, Mohanty S, Montgomery R, Krishnamurti L, Shaw A, Yildirim I. Unravelling the Immunological Enigma of Sickle Cell Disease: Current Understanding and Future Directions. Immunology 2025, 177: 445-456. PMID: 41387179, PMCID: PMC12826409, DOI: 10.1111/imm.70080.Peer-Reviewed Original ResearchMemory B cellsSickle cell diseaseImmune dysregulationT cellsB cellsChronic inflammationImmunological enigmaImmune activationClass-switched memory B cellsAntigen-specific T cell responsesAntigen-specific T cellsImmune responseCell diseaseAntigen-specific immune activationAntigen-specific immune responsesImmune-targeted therapiesSickle cell disease patientsT-cell countsT-cell abnormalitiesT-cell phenotypeMemory B cell differentiationT cell responsesB cell compartmentAdaptive immune dysfunctionSickle cell disease pathophysiology
Funding
Grants
Immune signatures of vaccine responses in children with sickle cell disease
- IRB/ID
- R01AI181379
- 12/01/2023 - 10/31/2028
- Funding Source
- National Institute of Allergy and Infectious Diseases