Immune response stability to the SARS-CoV-2 mRNA vaccine booster is influenced by differential splicing of HLA genes
Abstract Many molecular mechanisms that lead to the host antibody response to COVID-19 vaccines remain largely unknown. In this study, we used serum antibody detection combined with whole blood RNA-based transcriptome analysis to investigate variability in vaccine response in healthy recipients of a...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-59259-1 |
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| author | Cíntia Barros Santos-Rebouças Cristina dos Santos Ferreira Jeane de Souza Nogueira Otávio José Brustolini Luiz Gonzaga Paula de Almeida Alexandra Lehmkuhl Gerber Ana Paula de Campos Guimarães Rafael Mina Piergiorge Cláudio José Struchiner Luís Cristóvão Porto Ana Tereza Ribeiro de Vasconcelos |
| author_facet | Cíntia Barros Santos-Rebouças Cristina dos Santos Ferreira Jeane de Souza Nogueira Otávio José Brustolini Luiz Gonzaga Paula de Almeida Alexandra Lehmkuhl Gerber Ana Paula de Campos Guimarães Rafael Mina Piergiorge Cláudio José Struchiner Luís Cristóvão Porto Ana Tereza Ribeiro de Vasconcelos |
| author_sort | Cíntia Barros Santos-Rebouças |
| collection | DOAJ |
| description | Abstract Many molecular mechanisms that lead to the host antibody response to COVID-19 vaccines remain largely unknown. In this study, we used serum antibody detection combined with whole blood RNA-based transcriptome analysis to investigate variability in vaccine response in healthy recipients of a booster (third) dose schedule of the mRNA BNT162b2 vaccine against COVID-19. The cohort was divided into two groups: (1) low-stable individuals, with antibody concentration anti-SARS-CoV IgG S1 below 0.4 percentile at 180 days after boosting vaccination; and (2) high-stable individuals, with antibody values greater than 0.6 percentile of the range in the same period (median 9525 [185–80,000] AU/mL). Differential gene expression, expressed single nucleotide variants and insertions/deletions, differential splicing events, and allelic imbalance were explored to broaden our understanding of the immune response sustenance. Our analysis revealed a differential expression of genes with immunological functions in individuals with low antibody titers, compared to those with higher antibody titers, underscoring the fundamental importance of the innate immune response for boosting immunity. Our findings also provide new insights into the determinants of the immune response variability to the SARS-CoV-2 mRNA vaccine booster, highlighting the significance of differential splicing regulatory mechanisms, mainly concerning HLA alleles, in delineating vaccine immunogenicity. |
| first_indexed | 2024-04-24T07:17:42Z |
| format | Article |
| id | doaj.art-a86c39018f5a4e659cc99888fbbf8064 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T07:17:42Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a86c39018f5a4e659cc99888fbbf80642024-04-21T11:14:35ZengNature PortfolioScientific Reports2045-23222024-04-0114111410.1038/s41598-024-59259-1Immune response stability to the SARS-CoV-2 mRNA vaccine booster is influenced by differential splicing of HLA genesCíntia Barros Santos-Rebouças0Cristina dos Santos Ferreira1Jeane de Souza Nogueira2Otávio José Brustolini3Luiz Gonzaga Paula de Almeida4Alexandra Lehmkuhl Gerber5Ana Paula de Campos Guimarães6Rafael Mina Piergiorge7Cláudio José Struchiner8Luís Cristóvão Porto9Ana Tereza Ribeiro de Vasconcelos10Department of Genetics, Institute of Biology Roberto Alcantara Gomes, Rio de Janeiro State UniversityBioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTICHistocompatibility and Cryopreservation Laboratory, Rio de Janeiro State UniversityBioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTICBioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTICBioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTICBioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTICDepartment of Genetics, Institute of Biology Roberto Alcantara Gomes, Rio de Janeiro State UniversitySchool of Applied Mathematics, Getúlio Vargas FoundationHistocompatibility and Cryopreservation Laboratory, Rio de Janeiro State UniversityBioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTICAbstract Many molecular mechanisms that lead to the host antibody response to COVID-19 vaccines remain largely unknown. In this study, we used serum antibody detection combined with whole blood RNA-based transcriptome analysis to investigate variability in vaccine response in healthy recipients of a booster (third) dose schedule of the mRNA BNT162b2 vaccine against COVID-19. The cohort was divided into two groups: (1) low-stable individuals, with antibody concentration anti-SARS-CoV IgG S1 below 0.4 percentile at 180 days after boosting vaccination; and (2) high-stable individuals, with antibody values greater than 0.6 percentile of the range in the same period (median 9525 [185–80,000] AU/mL). Differential gene expression, expressed single nucleotide variants and insertions/deletions, differential splicing events, and allelic imbalance were explored to broaden our understanding of the immune response sustenance. Our analysis revealed a differential expression of genes with immunological functions in individuals with low antibody titers, compared to those with higher antibody titers, underscoring the fundamental importance of the innate immune response for boosting immunity. Our findings also provide new insights into the determinants of the immune response variability to the SARS-CoV-2 mRNA vaccine booster, highlighting the significance of differential splicing regulatory mechanisms, mainly concerning HLA alleles, in delineating vaccine immunogenicity.https://doi.org/10.1038/s41598-024-59259-1SARS-CoV-2Vaccine responseWhole blood transcriptomeImmune response variabilityAdmixed populationHuman leukocyte antigen |
| spellingShingle | Cíntia Barros Santos-Rebouças Cristina dos Santos Ferreira Jeane de Souza Nogueira Otávio José Brustolini Luiz Gonzaga Paula de Almeida Alexandra Lehmkuhl Gerber Ana Paula de Campos Guimarães Rafael Mina Piergiorge Cláudio José Struchiner Luís Cristóvão Porto Ana Tereza Ribeiro de Vasconcelos Immune response stability to the SARS-CoV-2 mRNA vaccine booster is influenced by differential splicing of HLA genes Scientific Reports SARS-CoV-2 Vaccine response Whole blood transcriptome Immune response variability Admixed population Human leukocyte antigen |
| title | Immune response stability to the SARS-CoV-2 mRNA vaccine booster is influenced by differential splicing of HLA genes |
| title_full | Immune response stability to the SARS-CoV-2 mRNA vaccine booster is influenced by differential splicing of HLA genes |
| title_fullStr | Immune response stability to the SARS-CoV-2 mRNA vaccine booster is influenced by differential splicing of HLA genes |
| title_full_unstemmed | Immune response stability to the SARS-CoV-2 mRNA vaccine booster is influenced by differential splicing of HLA genes |
| title_short | Immune response stability to the SARS-CoV-2 mRNA vaccine booster is influenced by differential splicing of HLA genes |
| title_sort | immune response stability to the sars cov 2 mrna vaccine booster is influenced by differential splicing of hla genes |
| topic | SARS-CoV-2 Vaccine response Whole blood transcriptome Immune response variability Admixed population Human leukocyte antigen |
| url | https://doi.org/10.1038/s41598-024-59259-1 |
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