Evaluation of the protective potential of antibody and T cell responses elicited by a novel preventative vaccine towards respiratory syncytial virus small hydrophobic protein
The small hydrophobic (SH) glycoprotein of human respiratory syncytial virus (RSV) is a transmembrane protein that is poorly accessible by antibodies on the virion but has an ectodomain (SHe) that is accessible and expressed on infected cells. The SHe from RSV strain A has been formulated in DPX, a...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2020-09-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2020.1756671 |
| _version_ | 1797677318265634816 |
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| author | Heather L. Torrey Valarmathy Kaliaperumal Yogesh Bramhecha Genevieve M. Weir Ann R. Falsey Edward E. Walsh Joanne M. Langley Bert Schepens Xavier Saelens Marianne M. Stanford |
| author_facet | Heather L. Torrey Valarmathy Kaliaperumal Yogesh Bramhecha Genevieve M. Weir Ann R. Falsey Edward E. Walsh Joanne M. Langley Bert Schepens Xavier Saelens Marianne M. Stanford |
| author_sort | Heather L. Torrey |
| collection | DOAJ |
| description | The small hydrophobic (SH) glycoprotein of human respiratory syncytial virus (RSV) is a transmembrane protein that is poorly accessible by antibodies on the virion but has an ectodomain (SHe) that is accessible and expressed on infected cells. The SHe from RSV strain A has been formulated in DPX, a unique delivery platform containing an adjuvant, and is being evaluated as an RSV vaccine candidate. The proposed mechanism of protection is the immune-mediated clearance of infected cells rather than neutralization of the virion. Our phase I clinical trial data clearly showed that vaccination resulted in robust antibody responses, but it was unclear if these immune responses have any correlation to immune responses to natural infection with RSV. Therefore, we embarked on this study to examine these immune responses in older adults with confirmed RSV infection. We compared vaccine-induced (DPX-RSV(A)) immune responses from participants in a Phase 1 clinical trial to paired acute and convalescent titers from older adults with symptomatic laboratory-confirmed RSV infection. Serum samples were tested for anti-SHe IgG titers and the isotypes determined. T cell responses were evaluated by IFN-γ ELISPOT. Anti-SHe titers were detected in 8 of 42 (19%) in the acute phase and 16 of 42 (38%) of convalescent serum samples. IgG1, IgG3, and IgA were the prevalent isotypes generated by both vaccination and infection. Antigen-specific T cell responses were detected in 9 of 16 (56%) of vaccinated participants. Depletion of CD4+ but not CD8+ T cells abrogated the IFN-γ ELISPOT response supporting the involvement of CD4+ T cells in the immune response to vaccination. The data showed that an immune response like that induced by DPX-RSV(A) could be seen in a subset of participants with confirmed RSV infection. These findings show that older adults with clinically significant infection as well as vaccinated adults generate a humoral response to SHe. The induction of both SHe-specific antibody and cellular responses support further clinical development of the DPX-RSV(A) vaccine. |
| first_indexed | 2024-03-11T22:42:52Z |
| format | Article |
| id | doaj.art-ffad43228ed34fcfa2f779ff8665e2cc |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:42:52Z |
| publishDate | 2020-09-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-ffad43228ed34fcfa2f779ff8665e2cc2023-09-22T08:51:48ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2020-09-011692007201710.1080/21645515.2020.17566711756671Evaluation of the protective potential of antibody and T cell responses elicited by a novel preventative vaccine towards respiratory syncytial virus small hydrophobic proteinHeather L. Torrey0Valarmathy Kaliaperumal1Yogesh Bramhecha2Genevieve M. Weir3Ann R. Falsey4Edward E. Walsh5Joanne M. Langley6Bert Schepens7Xavier Saelens8Marianne M. Stanford9IMV IncIMV IncIMV IncIMV IncUniversity of RochesterUniversity of RochesterCanadian Center for Vaccinology (IWK Health Centre and Nova Scotia Health Authority and Dalhousie University)VIB-UGent Center for Medical BiotechnologyVIB-UGent Center for Medical BiotechnologyIMV IncThe small hydrophobic (SH) glycoprotein of human respiratory syncytial virus (RSV) is a transmembrane protein that is poorly accessible by antibodies on the virion but has an ectodomain (SHe) that is accessible and expressed on infected cells. The SHe from RSV strain A has been formulated in DPX, a unique delivery platform containing an adjuvant, and is being evaluated as an RSV vaccine candidate. The proposed mechanism of protection is the immune-mediated clearance of infected cells rather than neutralization of the virion. Our phase I clinical trial data clearly showed that vaccination resulted in robust antibody responses, but it was unclear if these immune responses have any correlation to immune responses to natural infection with RSV. Therefore, we embarked on this study to examine these immune responses in older adults with confirmed RSV infection. We compared vaccine-induced (DPX-RSV(A)) immune responses from participants in a Phase 1 clinical trial to paired acute and convalescent titers from older adults with symptomatic laboratory-confirmed RSV infection. Serum samples were tested for anti-SHe IgG titers and the isotypes determined. T cell responses were evaluated by IFN-γ ELISPOT. Anti-SHe titers were detected in 8 of 42 (19%) in the acute phase and 16 of 42 (38%) of convalescent serum samples. IgG1, IgG3, and IgA were the prevalent isotypes generated by both vaccination and infection. Antigen-specific T cell responses were detected in 9 of 16 (56%) of vaccinated participants. Depletion of CD4+ but not CD8+ T cells abrogated the IFN-γ ELISPOT response supporting the involvement of CD4+ T cells in the immune response to vaccination. The data showed that an immune response like that induced by DPX-RSV(A) could be seen in a subset of participants with confirmed RSV infection. These findings show that older adults with clinically significant infection as well as vaccinated adults generate a humoral response to SHe. The induction of both SHe-specific antibody and cellular responses support further clinical development of the DPX-RSV(A) vaccine.http://dx.doi.org/10.1080/21645515.2020.1756671respiratory syncytial virusvaccinet cellb cellimmunotherapyantibodynatural infectionimmunizationagedadult |
| spellingShingle | Heather L. Torrey Valarmathy Kaliaperumal Yogesh Bramhecha Genevieve M. Weir Ann R. Falsey Edward E. Walsh Joanne M. Langley Bert Schepens Xavier Saelens Marianne M. Stanford Evaluation of the protective potential of antibody and T cell responses elicited by a novel preventative vaccine towards respiratory syncytial virus small hydrophobic protein Human Vaccines & Immunotherapeutics respiratory syncytial virus vaccine t cell b cell immunotherapy antibody natural infection immunization aged adult |
| title | Evaluation of the protective potential of antibody and T cell responses elicited by a novel preventative vaccine towards respiratory syncytial virus small hydrophobic protein |
| title_full | Evaluation of the protective potential of antibody and T cell responses elicited by a novel preventative vaccine towards respiratory syncytial virus small hydrophobic protein |
| title_fullStr | Evaluation of the protective potential of antibody and T cell responses elicited by a novel preventative vaccine towards respiratory syncytial virus small hydrophobic protein |
| title_full_unstemmed | Evaluation of the protective potential of antibody and T cell responses elicited by a novel preventative vaccine towards respiratory syncytial virus small hydrophobic protein |
| title_short | Evaluation of the protective potential of antibody and T cell responses elicited by a novel preventative vaccine towards respiratory syncytial virus small hydrophobic protein |
| title_sort | evaluation of the protective potential of antibody and t cell responses elicited by a novel preventative vaccine towards respiratory syncytial virus small hydrophobic protein |
| topic | respiratory syncytial virus vaccine t cell b cell immunotherapy antibody natural infection immunization aged adult |
| url | http://dx.doi.org/10.1080/21645515.2020.1756671 |
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