Associations of human leukocyte antigen with neutralizing antibody titers in a tetravalent dengue vaccine phase 2 efficacy trial in Thailand

Rasmi Thomas, Danaya Chansinghakul*, Kriengsak Limkittikul, Peter B. Gilbert, Weerawan Hattasingh, Zoe Moodie, Shida Shangguan, Carina Frago, Wut Dulyachai, Shuying Sue Li, Richard G. Jarman, Aviva Geretz, Alain Bouckenooghe, Arunee Sabchareon, Michal Juraska, Philip Ehrenberg, Nelson L. Michael, Fabrice Bailleux, Chris Bryant, Sanjay Gurunathan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The recombinant, live, attenuated, tetravalent dengue vaccine CYD-TDV has shown efficacy against all four dengue serotypes. In this exploratory study (CYD59, NCT02827162), we evaluated potential associations of host human leukocyte antigen (HLA) alleles with dengue antibody responses, CYD-TDV vaccine efficacy, and virologically-confirmed dengue (VCD) cases. Children 4–11 years old, who previously completed a phase 2b efficacy study of CYD-TDV in a single center in Thailand, were included in the study. Genotyping of HLA class I and II loci was performed by next-generation sequencing from DNA obtained from 335 saliva samples. Dengue neutralizing antibody titers (NAb) were assessed as a correlate of risk and protection. Regression analyses were used to assess associations between HLA alleles and NAb responses, vaccine efficacy, and dengue outcomes. Month 13 NAb log geometric mean titers (GMTs) were associated with decreased risk of VCD. In the vaccine group, HLA-DRB1*11 was significantly associated with higher NAb log GMT levels (beta: 0.76; p = 0.002, q = 0.13). Additionally, in the absence of vaccination, HLA associations were observed between the presence of DPB1*03:01 and increased NAb log GMT levels (beta: 1.24; p = 0.005, q = 0.17), and between DPB1*05:01 and reduced NAb log GMT levels (beta: −1.1; p = 0.001, q = 0.07). This study suggests associations of HLA alleles with NAb titers in the context of dengue outcomes. This study was registered with clinicaltrials.gov: NCT02827162.

Original languageEnglish
Pages (from-to)53-60
Number of pages8
JournalHuman Immunology
Volume83
Issue number1
DOIs
StatePublished - Jan 2022
Externally publishedYes

Keywords

  • CYD-TDV
  • Dengue
  • HLA
  • Human leukocyte antigen
  • Vaccine efficacy

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