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
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 postvacci...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-05-01
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| Series: | PLoS Biology |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154185/?tool=EBI |
| _version_ | 1818539909287247872 |
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| author | Ayesa Syenina Esther S. Gan Justin Z. N. Toh Ruklanthi de Alwis Lowell Z. Lin Christine Y. L. Tham Jia Xin Yee Yan Shan Leong Huizhen Sam Charlene Cheong Yii Ean Teh Ian L. E. Wee Dorothy H. L. Ng Kuan Rong Chan Jean X. Y. Sim Shirin Kalimuddin Eugenia Z. Ong Jenny G. Low Eng Eong Ooi |
| author_facet | Ayesa Syenina Esther S. Gan Justin Z. N. Toh Ruklanthi de Alwis Lowell Z. Lin Christine Y. L. Tham Jia Xin Yee Yan Shan Leong Huizhen Sam Charlene Cheong Yii Ean Teh Ian L. E. Wee Dorothy H. L. Ng Kuan Rong Chan Jean X. Y. Sim Shirin Kalimuddin Eugenia Z. Ong Jenny G. Low Eng Eong Ooi |
| author_sort | Ayesa Syenina |
| collection | DOAJ |
| description | 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. Systemic adverse events, such as post-vaccination fatigue, are prevalent consequences of mRNA vaccination; why is this? This study shows that higher baseline expression of T and NK cell genes increases susceptibility to fatigue after mRNA vaccination, and that altering the route of vaccination may reduce the incidence of mRNA vaccine-associated systemic adverse events. |
| first_indexed | 2024-12-11T21:48:21Z |
| format | Article |
| id | doaj.art-ecfcaa6f536c4157ba77ecce6b10848c |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-11T21:48:21Z |
| publishDate | 2022-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-ecfcaa6f536c4157ba77ecce6b10848c2022-12-22T00:49:33ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-05-01205Adverse 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 genesAyesa SyeninaEsther S. GanJustin Z. N. TohRuklanthi de AlwisLowell Z. LinChristine Y. L. ThamJia Xin YeeYan Shan LeongHuizhen SamCharlene CheongYii Ean TehIan L. E. WeeDorothy H. L. NgKuan Rong ChanJean X. Y. SimShirin KalimuddinEugenia Z. OngJenny G. LowEng Eong OoiEnsuring 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. Systemic adverse events, such as post-vaccination fatigue, are prevalent consequences of mRNA vaccination; why is this? This study shows that higher baseline expression of T and NK cell genes increases susceptibility to fatigue after mRNA vaccination, and that altering the route of vaccination may reduce the incidence of mRNA vaccine-associated systemic adverse events.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154185/?tool=EBI |
| spellingShingle | Ayesa Syenina Esther S. Gan Justin Z. N. Toh Ruklanthi de Alwis Lowell Z. Lin Christine Y. L. Tham Jia Xin Yee Yan Shan Leong Huizhen Sam Charlene Cheong Yii Ean Teh Ian L. E. Wee Dorothy H. L. Ng Kuan Rong Chan Jean X. Y. Sim Shirin Kalimuddin Eugenia Z. Ong Jenny G. Low Eng Eong Ooi 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 PLoS Biology |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154185/?tool=EBI |
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