Associations of human leukocyte antigen with neutralizing antibody titers in a tetravalent dengue vaccine phase 2 efficacy trial in Thailand
3
Issued Date
2022-01-01
Resource Type
ISSN
01988859
eISSN
18791166
Scopus ID
2-s2.0-85116804608
Pubmed ID
34635391
Journal Title
Human Immunology
Volume
83
Issue
1
Start Page
53
End Page
60
Rights Holder(s)
SCOPUS
Bibliographic Citation
Human Immunology Vol.83 No.1 (2022) , 53-60
Suggested Citation
Thomas R., Chansinghakul D., Limkittikul K., Gilbert P.B., Hattasingh W., Moodie Z., Shangguan S., Frago C., Dulyachai W., Li S.S., Jarman R.G., Geretz A., Bouckenooghe A., Sabchareon A., Juraska M., Ehrenberg P., Michael N.L., Bailleux F., Bryant C., Gurunathan S. Associations of human leukocyte antigen with neutralizing antibody titers in a tetravalent dengue vaccine phase 2 efficacy trial in Thailand. Human Immunology Vol.83 No.1 (2022) , 53-60. 60. doi:10.1016/j.humimm.2021.09.006 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/85065
Title
Associations of human leukocyte antigen with neutralizing antibody titers in a tetravalent dengue vaccine phase 2 efficacy trial in Thailand
Other Contributor(s)
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.