PMID- 28978802
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20190729
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 2
IP  - 19
DP  - 2017 Oct 5
TI  - Early molecular correlates of adverse events following yellow fever vaccination.
LID - 96031 [pii]
LID - 10.1172/jci.insight.96031 [doi]
LID - e96031
AB  - The innate immune response shapes the development of adaptive immunity following 
      infections and vaccination. However, it can also induce symptoms such as fever 
      and myalgia, leading to the possibility that the molecular basis of 
      immunogenicity and reactogenicity of vaccination are inseparably linked. To test 
      this possibility, we used the yellow fever live-attenuated vaccine (YFLAV) as a 
      model to study the molecular correlates of reactogenicity or adverse events 
      (AEs). We analyzed the outcome of 68 adults who completed a YFLAV clinical trial, 
      of which 43 (63.2%) reported systemic AEs. Through whole-genome profiling of 
      blood collected before and after YFLAV dosing, we observed that activation of 
      innate immune genes at day 1, but not day 3 after vaccination, was directly 
      correlated with AEs. These findings contrast with the gene expression profile at 
      day 3 that we and others have previously shown to be correlated with 
      immunogenicity. We conclude that although the innate immune response is a 
      double-edged sword, its expression that induces AEs is temporally distinct from 
      that which engenders robust immunity. The use of genomic profiling thus provides 
      molecular insights into the biology of AEs that potentially forms a basis for the 
      development of safer vaccines.
FAU - Chan, Candice Yy
AU  - Chan CY
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
AD  - Department of Infectious Diseases, Singapore General Hospital, Singapore.
FAU - Chan, Kuan Rong
AU  - Chan KR
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
FAU - Chua, Camillus Jh
AU  - Chua CJ
AD  - SingHealth Translational Immunology and Inflammation Centre (STIIC), Singapore.
FAU - Nur Hazirah, Sharifah
AU  - Nur Hazirah S
AD  - SingHealth Translational Immunology and Inflammation Centre (STIIC), Singapore.
FAU - Ghosh, Sujoy
AU  - Ghosh S
AD  - Centre for Computational Biology, Duke-NUS Medical School, Singapore.
FAU - Ooi, Eng Eong
AU  - Ooi EE
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
AD  - Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, 
      National University of Singapore, Singapore.
AD  - Saw Swee Hock School of Public Health, National University of Singapore, 
      Singapore.
AD  - Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance 
      for Research & Technology (SMART), Singapore.
FAU - Low, Jenny G
AU  - Low JG
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
AD  - Department of Infectious Diseases, Singapore General Hospital, Singapore.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20171005
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - 0 (Antibodies, Viral)
RN  - 0 (Yellow Fever Vaccine)
MH  - Adult
MH  - Antibodies, Viral/blood
MH  - Central Nervous System Diseases/etiology/genetics/immunology
MH  - Female
MH  - Gene Expression Profiling/methods
MH  - Humans
MH  - Immunity, Innate/genetics/immunology
MH  - Male
MH  - Middle Aged
MH  - Musculoskeletal Diseases/etiology/genetics/immunology
MH  - Up-Regulation/immunology
MH  - Vaccination/*adverse effects
MH  - Viremia/immunology
MH  - Yellow Fever/immunology/*prevention & control/virology
MH  - Yellow Fever Vaccine/*adverse effects/immunology
MH  - Yellow fever virus/immunology/isolation & purification
MH  - Young Adult
PMC - PMC5841882
COIS- Conflict of interest: The authors have declared that no conflict of interest 
      exists.
EDAT- 2017/10/06 06:00
MHDA- 2019/07/30 06:00
PMCR- 2017/10/05
CRDT- 2017/10/06 06:00
PHST- 2017/07/05 00:00 [received]
PHST- 2017/08/29 00:00 [accepted]
PHST- 2017/10/06 06:00 [entrez]
PHST- 2017/10/06 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2017/10/05 00:00 [pmc-release]
AID - 96031 [pii]
AID - 10.1172/jci.insight.96031 [doi]
PST - epublish
SO  - JCI Insight. 2017 Oct 5;2(19):e96031. doi: 10.1172/jci.insight.96031.