TY - JOUR
T1 - Associations of human leukocyte antigen with neutralizing antibody titers in a tetravalent dengue vaccine phase 2 efficacy trial in Thailand
AU - Thomas, Rasmi
AU - Chansinghakul, Danaya
AU - Limkittikul, Kriengsak
AU - Gilbert, Peter B.
AU - Hattasingh, Weerawan
AU - Moodie, Zoe
AU - Shangguan, Shida
AU - Frago, Carina
AU - Dulyachai, Wut
AU - Li, Shuying Sue
AU - Jarman, Richard G.
AU - Geretz, Aviva
AU - Bouckenooghe, Alain
AU - Sabchareon, Arunee
AU - Juraska, Michal
AU - Ehrenberg, Philip
AU - Michael, Nelson L.
AU - Bailleux, Fabrice
AU - Bryant, Chris
AU - Gurunathan, Sanjay
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
KW - CYD-TDV
KW - Dengue
KW - HLA
KW - Human leukocyte antigen
KW - Vaccine efficacy
UR - http://www.scopus.com/inward/record.url?scp=85116804608&partnerID=8YFLogxK
U2 - 10.1016/j.humimm.2021.09.006
DO - 10.1016/j.humimm.2021.09.006
M3 - Article
C2 - 34635391
AN - SCOPUS:85116804608
SN - 0198-8859
VL - 83
SP - 53
EP - 60
JO - Human Immunology
JF - Human Immunology
IS - 1
ER -