Prior dengue virus serotype 3 infection modulates subsequent plasmablast responses to Zika virus infection in rhesus macaques
ABSTRACTImmunodominant and highly conserved flavivirus envelope proteins can trigger cross-reactive IgG antibodies against related flaviviruses, which shapes subsequent protection or disease severity. This study examined how prior dengue serotype 3 (DENV-3) infection affects subsequent Zika virus (Z...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2024-03-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03160-23 |
| _version_ | 1797263250713214976 |
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| author | Tulika Singh Itzayana G. Miller Sravani Venkatayogi Helen Webster Holly J. Heimsath Josh A. Eudailey Dawn M. Dudley Amit Kumar Riley J. Mangan Amelia Thein Matthew T. Aliota Christina M. Newman Mariel S. Mohns Meghan E. Breitbach Madison Berry Thomas C. Friedrich Kevin Wiehe David H. O'Connor Sallie R. Permar |
| author_facet | Tulika Singh Itzayana G. Miller Sravani Venkatayogi Helen Webster Holly J. Heimsath Josh A. Eudailey Dawn M. Dudley Amit Kumar Riley J. Mangan Amelia Thein Matthew T. Aliota Christina M. Newman Mariel S. Mohns Meghan E. Breitbach Madison Berry Thomas C. Friedrich Kevin Wiehe David H. O'Connor Sallie R. Permar |
| author_sort | Tulika Singh |
| collection | DOAJ |
| description | ABSTRACTImmunodominant and highly conserved flavivirus envelope proteins can trigger cross-reactive IgG antibodies against related flaviviruses, which shapes subsequent protection or disease severity. This study examined how prior dengue serotype 3 (DENV-3) infection affects subsequent Zika virus (ZIKV) plasmablast responses in rhesus macaques (n = 4). We found that prior DENV-3 infection was not associated with diminished ZIKV-neutralizing antibodies or magnitude of plasmablast activation. Rather, characterization of 363 plasmablasts and their derivative 177 monoclonal antibody supernatants from acute ZIKV infection revealed that prior DENV-3 infection was associated with a differential isotype distribution toward IgG, lower somatic hypermutation, and lesser B cell receptor variable gene diversity as compared with repeat ZIKV challenge. We did not find long-lasting DENV-3 cross-reactive IgG after a ZIKV infection but did find persistent ZIKV-binding cross-reactive IgG after a DENV-3 infection, suggesting non-reciprocal cross-reactive immunity. Infection with ZIKV after DENV-3 boosted pre-existing DENV-3-neutralizing antibodies by two- to threefold, demonstrating immune imprinting. These findings suggest that the order of DENV and ZIKV infections has impact on the quality of early B cell immunity which has implications for optimal immunization strategies.IMPORTANCEThe Zika virus epidemic of 2015–2016 in the Americas revealed that this mosquito-transmitted virus could be congenitally transmitted during pregnancy and cause birth defects in newborns. Currently, there are no interventions to mitigate this disease and Zika virus is likely to re-emerge. Understanding how protective antibody responses are generated against Zika virus can help in the development of a safe and effective vaccine. One main challenge is that Zika virus co-circulates with related viruses like dengue, such that prior exposure to one can generate cross-reactive antibodies against the other which may enhance infection and disease from the second virus. In this study, we sought to understand how prior dengue virus infection impacts subsequent immunity to Zika virus by single-cell sequencing of antibody producing cells in a second Zika virus infection. Identifying specific qualities of Zika virus immunity that are modulated by prior dengue virus immunity will enable optimal immunization strategies. |
| first_indexed | 2024-04-25T00:10:02Z |
| format | Article |
| id | doaj.art-496d519ecdd14e718fa10a683dc6b9bf |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-25T00:10:02Z |
| publishDate | 2024-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-496d519ecdd14e718fa10a683dc6b9bf2024-03-13T14:01:05ZengAmerican Society for MicrobiologymBio2150-75112024-03-0115310.1128/mbio.03160-23Prior dengue virus serotype 3 infection modulates subsequent plasmablast responses to Zika virus infection in rhesus macaquesTulika Singh0Itzayana G. Miller1Sravani Venkatayogi2Helen Webster3Holly J. Heimsath4Josh A. Eudailey5Dawn M. Dudley6Amit Kumar7Riley J. Mangan8Amelia Thein9Matthew T. Aliota10Christina M. Newman11Mariel S. Mohns12Meghan E. Breitbach13Madison Berry14Thomas C. Friedrich15Kevin Wiehe16David H. O'Connor17Sallie R. Permar18Human Vaccine Institute, School of Medicine, Duke University, Durham, North Carolina, USADepartment of Pediatrics, Weill Cornell Medicine, New York, USAHuman Vaccine Institute, School of Medicine, Duke University, Durham, North Carolina, USAHuman Vaccine Institute, School of Medicine, Duke University, Durham, North Carolina, USAHuman Vaccine Institute, School of Medicine, Duke University, Durham, North Carolina, USAHuman Vaccine Institute, School of Medicine, Duke University, Durham, North Carolina, USADepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USAHuman Vaccine Institute, School of Medicine, Duke University, Durham, North Carolina, USAHuman Vaccine Institute, School of Medicine, Duke University, Durham, North Carolina, USADepartment of Pediatrics, Weill Cornell Medicine, New York, USADepartment of Veterinary and Biomedical Sciences, University of Minnesota, Twin Cities, St. Paul, Minnesota, USADepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USADepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USADepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USAHuman Vaccine Institute, School of Medicine, Duke University, Durham, North Carolina, USADepartment of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USAHuman Vaccine Institute, School of Medicine, Duke University, Durham, North Carolina, USADepartment of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USAHuman Vaccine Institute, School of Medicine, Duke University, Durham, North Carolina, USAABSTRACTImmunodominant and highly conserved flavivirus envelope proteins can trigger cross-reactive IgG antibodies against related flaviviruses, which shapes subsequent protection or disease severity. This study examined how prior dengue serotype 3 (DENV-3) infection affects subsequent Zika virus (ZIKV) plasmablast responses in rhesus macaques (n = 4). We found that prior DENV-3 infection was not associated with diminished ZIKV-neutralizing antibodies or magnitude of plasmablast activation. Rather, characterization of 363 plasmablasts and their derivative 177 monoclonal antibody supernatants from acute ZIKV infection revealed that prior DENV-3 infection was associated with a differential isotype distribution toward IgG, lower somatic hypermutation, and lesser B cell receptor variable gene diversity as compared with repeat ZIKV challenge. We did not find long-lasting DENV-3 cross-reactive IgG after a ZIKV infection but did find persistent ZIKV-binding cross-reactive IgG after a DENV-3 infection, suggesting non-reciprocal cross-reactive immunity. Infection with ZIKV after DENV-3 boosted pre-existing DENV-3-neutralizing antibodies by two- to threefold, demonstrating immune imprinting. These findings suggest that the order of DENV and ZIKV infections has impact on the quality of early B cell immunity which has implications for optimal immunization strategies.IMPORTANCEThe Zika virus epidemic of 2015–2016 in the Americas revealed that this mosquito-transmitted virus could be congenitally transmitted during pregnancy and cause birth defects in newborns. Currently, there are no interventions to mitigate this disease and Zika virus is likely to re-emerge. Understanding how protective antibody responses are generated against Zika virus can help in the development of a safe and effective vaccine. One main challenge is that Zika virus co-circulates with related viruses like dengue, such that prior exposure to one can generate cross-reactive antibodies against the other which may enhance infection and disease from the second virus. In this study, we sought to understand how prior dengue virus infection impacts subsequent immunity to Zika virus by single-cell sequencing of antibody producing cells in a second Zika virus infection. Identifying specific qualities of Zika virus immunity that are modulated by prior dengue virus immunity will enable optimal immunization strategies.https://journals.asm.org/doi/10.1128/mbio.03160-23Zika virusdengue virusplasmablastB cellneutralizing antibodies |
| spellingShingle | Tulika Singh Itzayana G. Miller Sravani Venkatayogi Helen Webster Holly J. Heimsath Josh A. Eudailey Dawn M. Dudley Amit Kumar Riley J. Mangan Amelia Thein Matthew T. Aliota Christina M. Newman Mariel S. Mohns Meghan E. Breitbach Madison Berry Thomas C. Friedrich Kevin Wiehe David H. O'Connor Sallie R. Permar Prior dengue virus serotype 3 infection modulates subsequent plasmablast responses to Zika virus infection in rhesus macaques mBio Zika virus dengue virus plasmablast B cell neutralizing antibodies |
| title | Prior dengue virus serotype 3 infection modulates subsequent plasmablast responses to Zika virus infection in rhesus macaques |
| title_full | Prior dengue virus serotype 3 infection modulates subsequent plasmablast responses to Zika virus infection in rhesus macaques |
| title_fullStr | Prior dengue virus serotype 3 infection modulates subsequent plasmablast responses to Zika virus infection in rhesus macaques |
| title_full_unstemmed | Prior dengue virus serotype 3 infection modulates subsequent plasmablast responses to Zika virus infection in rhesus macaques |
| title_short | Prior dengue virus serotype 3 infection modulates subsequent plasmablast responses to Zika virus infection in rhesus macaques |
| title_sort | prior dengue virus serotype 3 infection modulates subsequent plasmablast responses to zika virus infection in rhesus macaques |
| topic | Zika virus dengue virus plasmablast B cell neutralizing antibodies |
| url | https://journals.asm.org/doi/10.1128/mbio.03160-23 |
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