PMID- 35639676
OWN - NLM
STAT- MEDLINE
DCOM- 20220602
LR  - 20220716
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 20
IP  - 5
DP  - 2022 May
TI  - Adverse effects following anti-COVID-19 vaccination with mRNA-based BNT162b2 are 
      alleviated by altering the route of administration and correlate with baseline 
      enrichment of T and NK cell genes.
PG  - e3001643
LID - 10.1371/journal.pbio.3001643 [doi]
LID - e3001643
AB  - Ensuring high vaccination and even booster vaccination coverage is critical in 
      preventing severe Coronavirus Disease 2019 (COVID-19). Among the various COVID-19 
      vaccines currently in use, the mRNA vaccines have shown remarkable effectiveness. 
      However, systemic adverse events (AEs), such as postvaccination fatigue, are 
      prevalent following mRNA vaccination, and the underpinnings of which are not 
      understood. Herein, we found that higher baseline expression of genes related to 
      T and NK cell exhaustion and suppression were positively correlated with the 
      development of moderately severe fatigue after Pfizer-BioNTech BNT162b2 
      vaccination; increased expression of genes associated with T and NK cell 
      exhaustion and suppression reacted to vaccination were associated with greater 
      levels of innate immune activation at 1 day postvaccination. We further found, in 
      a mouse model, that altering the route of vaccination from intramuscular (i.m.) 
      to subcutaneous (s.c.) could lessen the pro-inflammatory response and 
      correspondingly the extent of systemic AEs; the humoral immune response to 
      BNT162b2 vaccination was not compromised. Instead, it is possible that the s.c. 
      route could improve cytotoxic CD8 T-cell responses to BNT162b2 vaccination. Our 
      findings thus provide a glimpse of the molecular basis of postvaccination fatigue 
      from mRNA vaccination and suggest a readily translatable solution to minimize 
      systemic AEs.
FAU - Syenina, Ayesa
AU  - Syenina A
AUID- ORCID: 0000-0003-0061-8401
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
AD  - Viral Research and Experimental Medicine Centre, SingHealth Duke-NUS Academic 
      Medical Centre, Singapore.
FAU - Gan, Esther S
AU  - Gan ES
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
FAU - Toh, Justin Z N
AU  - Toh JZN
AD  - Viral Research and Experimental Medicine Centre, SingHealth Duke-NUS Academic 
      Medical Centre, Singapore.
AD  - School of Life Sciences, Nanyang Polytechnic, Singapore.
FAU - de Alwis, Ruklanthi
AU  - de Alwis R
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
AD  - Viral Research and Experimental Medicine Centre, SingHealth Duke-NUS Academic 
      Medical Centre, Singapore.
FAU - Lin, Lowell Z
AU  - Lin LZ
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
FAU - Tham, Christine Y L
AU  - Tham CYL
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
AD  - Viral Research and Experimental Medicine Centre, SingHealth Duke-NUS Academic 
      Medical Centre, Singapore.
FAU - Yee, Jia Xin
AU  - Yee JX
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
AD  - Viral Research and Experimental Medicine Centre, SingHealth Duke-NUS Academic 
      Medical Centre, Singapore.
FAU - Leong, Yan Shan
AU  - Leong YS
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
AD  - Viral Research and Experimental Medicine Centre, SingHealth Duke-NUS Academic 
      Medical Centre, Singapore.
FAU - Sam, Huizhen
AU  - Sam H
AD  - Department of Infectious Diseases, Singapore General Hospital, Singapore.
FAU - Cheong, Charlene
AU  - Cheong C
AD  - Department of Infectious Diseases, Singapore General Hospital, Singapore.
FAU - Teh, Yii Ean
AU  - Teh YE
AD  - Department of Infectious Diseases, Singapore General Hospital, Singapore.
FAU - Wee, Ian L E
AU  - Wee ILE
AD  - Department of Infectious Diseases, Singapore General Hospital, Singapore.
FAU - Ng, Dorothy H L
AU  - Ng DHL
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 - Sim, Jean X Y
AU  - Sim JXY
AD  - Department of Infectious Diseases, Singapore General Hospital, Singapore.
FAU - Kalimuddin, Shirin
AU  - Kalimuddin S
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
AD  - Department of Infectious Diseases, Singapore General Hospital, Singapore.
FAU - Ong, Eugenia Z
AU  - Ong EZ
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
AD  - Viral Research and Experimental Medicine Centre, SingHealth Duke-NUS Academic 
      Medical Centre, Singapore.
FAU - Low, Jenny G
AU  - Low JG
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
AD  - Viral Research and Experimental Medicine Centre, SingHealth Duke-NUS Academic 
      Medical Centre, Singapore.
AD  - Department of Infectious Diseases, Singapore General Hospital, Singapore.
FAU - Ooi, Eng Eong
AU  - Ooi EE
AUID- ORCID: 0000-0002-0520-1544
AD  - Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
AD  - Viral Research and Experimental Medicine Centre, SingHealth Duke-NUS Academic 
      Medical Centre, Singapore.
AD  - Department of Infectious Diseases, Singapore General Hospital, Singapore.
AD  - Saw Swee Hock School of Public Health, National University of Singapore, 
      Singapore.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220531
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (COVID-19 Vaccines)
RN  - 0 (RNA, Messenger)
RN  - N38TVC63NU (BNT162 Vaccine)
SB  - IM
MH  - Animals
MH  - BNT162 Vaccine
MH  - *COVID-19/prevention & control
MH  - COVID-19 Vaccines/adverse effects
MH  - Fatigue/etiology
MH  - Humans
MH  - Killer Cells, Natural
MH  - Mice
MH  - RNA, Messenger/genetics
MH  - Vaccination/adverse effects
PMC - PMC9154185
COIS- The authors have declared no competing interests exists.
EDAT- 2022/06/01 06:00
MHDA- 2022/06/03 06:00
PMCR- 2022/05/31
CRDT- 2022/05/31 16:09
PHST- 2022/03/01 00:00 [received]
PHST- 2022/04/22 00:00 [accepted]
PHST- 2022/05/31 16:09 [entrez]
PHST- 2022/06/01 06:00 [pubmed]
PHST- 2022/06/03 06:00 [medline]
PHST- 2022/05/31 00:00 [pmc-release]
AID - PBIOLOGY-D-22-00476 [pii]
AID - 10.1371/journal.pbio.3001643 [doi]
PST - epublish
SO  - PLoS Biol. 2022 May 31;20(5):e3001643. doi: 10.1371/journal.pbio.3001643. 
      eCollection 2022 May.