PMID- 34635391
OWN - NLM
STAT- MEDLINE
DCOM- 20220316
LR  - 20231003
IS  - 1879-1166 (Electronic)
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 83
IP  - 1
DP  - 2022 Jan
TI  - Associations of human leukocyte antigen with neutralizing antibody titers in a 
      tetravalent dengue vaccine phase 2 efficacy trial in Thailand.
PG  - 53-60
LID - S0198-8859(21)00236-6 [pii]
LID - 10.1016/j.humimm.2021.09.006 [doi]
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.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Thomas, Rasmi
AU  - Thomas R
AD  - US Military HIV Research Program, Walter Reed Army Institute of Research, Silver 
      Spring, MD 20910, USA.
FAU - Chansinghakul, Danaya
AU  - Chansinghakul D
AD  - Sanofi Pasteur Clinical Sciences, Bangkok 10330, Thailand. Electronic address: 
      Danaya.Chansinghakul@sanofi.com.
FAU - Limkittikul, Kriengsak
AU  - Limkittikul K
AD  - Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol 
      University, Bangkok 73170, Thailand.
FAU - Gilbert, Peter B
AU  - Gilbert PB
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA 98109-1024, USA.
FAU - Hattasingh, Weerawan
AU  - Hattasingh W
AD  - Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol 
      University, Bangkok 73170, Thailand.
FAU - Moodie, Zoe
AU  - Moodie Z
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA 98109-1024, USA.
FAU - Shangguan, Shida
AU  - Shangguan S
AD  - US Military HIV Research Program, Walter Reed Army Institute of Research, Silver 
      Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of 
      Military Medicine, Bethesda, MD 20817, USA.
FAU - Frago, Carina
AU  - Frago C
AD  - Global Clinical Sciences, Sanofi Pasteur, 048580, Singapore.
FAU - Dulyachai, Wut
AU  - Dulyachai W
AD  - Ratchaburi Hospital, Amphoe Muang Ratchaburi, 70000, Thailand.
FAU - Li, Shuying Sue
AU  - Li SS
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA 98109-1024, USA.
FAU - Jarman, Richard G
AU  - Jarman RG
AD  - Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 
      20910, USA.
FAU - Geretz, Aviva
AU  - Geretz A
AD  - US Military HIV Research Program, Walter Reed Army Institute of Research, Silver 
      Spring, MD 20910, USA; Henry M. Jackson Foundation for the Advancement of 
      Military Medicine, Bethesda, MD 20817, USA.
FAU - Bouckenooghe, Alain
AU  - Bouckenooghe A
AD  - Global Clinical Sciences, Sanofi Pasteur, 048580, Singapore.
FAU - Sabchareon, Arunee
AU  - Sabchareon A
AD  - Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol 
      University, Bangkok 73170, Thailand.
FAU - Juraska, Michal
AU  - Juraska M
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA 98109-1024, USA.
FAU - Ehrenberg, Philip
AU  - Ehrenberg P
AD  - US Military HIV Research Program, Walter Reed Army Institute of Research, Silver 
      Spring, MD 20910, USA.
FAU - Michael, Nelson L
AU  - Michael NL
AD  - US Military HIV Research Program, Walter Reed Army Institute of Research, Silver 
      Spring, MD 20910, USA.
FAU - Bailleux, Fabrice
AU  - Bailleux F
AD  - Sanofi Pasteur, Marcy l'Etoile 69280, France.
FAU - Bryant, Chris
AU  - Bryant C
AD  - The Emmes Company, Rockville, MD 20850, USA.
FAU - Gurunathan, Sanjay
AU  - Gurunathan S
AD  - Sanofi Pasteur, Swiftwater, PA 18370, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02827162
GR  - R37 AI054165/AI/NIAID NIH HHS/United States
GR  - UM1 AI068635/AI/NIAID NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20211008
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Dengue Vaccines)
RN  - 0 (HLA Antigens)
RN  - 0 (Vaccines, Combined)
SB  - IM
MH  - Antibodies, Neutralizing
MH  - Antibodies, Viral
MH  - Child
MH  - Child, Preschool
MH  - *Dengue/prevention & control
MH  - *Dengue Vaccines
MH  - *Dengue Virus
MH  - HLA Antigens/genetics
MH  - Humans
MH  - Thailand
MH  - Vaccines, Combined
PMC - PMC10536818
MID - NIHMS1927828
OTO - NOTNLM
OT  - CYD-TDV
OT  - Dengue
OT  - HLA
OT  - Human leukocyte antigen
OT  - Vaccine efficacy
COIS- Declaration of Competing Interest D.C., C.F., A.B., F.B., S.G. are employees of 
      Sanofi Pasteur and may hold shares and/or stock options in the company. R.T., 
      K.L., W.H., S.S., W.T., R.G.J., A.G., A.S., P.E., N.L.M., C.B. have no conflict 
      of interest to declare. P.B.G., Z.M., M.J., and S.S.L. received a contract from 
      Sanofi Pasteur to conduct the statistical analysis work.
EDAT- 2021/10/13 06:00
MHDA- 2022/03/17 06:00
PMCR- 2023/09/28
CRDT- 2021/10/12 05:47
PHST- 2021/03/01 00:00 [received]
PHST- 2021/08/12 00:00 [revised]
PHST- 2021/09/20 00:00 [accepted]
PHST- 2021/10/13 06:00 [pubmed]
PHST- 2022/03/17 06:00 [medline]
PHST- 2021/10/12 05:47 [entrez]
PHST- 2023/09/28 00:00 [pmc-release]
AID - S0198-8859(21)00236-6 [pii]
AID - 10.1016/j.humimm.2021.09.006 [doi]
PST - ppublish
SO  - Hum Immunol. 2022 Jan;83(1):53-60. doi: 10.1016/j.humimm.2021.09.006. Epub 2021 
      Oct 8.