Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice
We investigated the long-term immune profiles of dose-sparing, AS03-adjuvanted vaccines compared to a traditional high-dose, unadjuvated influenza vaccine formulation. BALB/c mice received 2 IM injections of influenza A/Uruguay/716/2007 (H3N2) split vaccine antigen: high-dose (HD) (3 µg hemagglutini...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-03-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2016.1241360 |
| _version_ | 1827807730526584832 |
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| author | Karen K. Yam Angela Brewer Virginie Bleau Édith Beaulieu Corey P. Mallett Brian J. Ward |
| author_facet | Karen K. Yam Angela Brewer Virginie Bleau Édith Beaulieu Corey P. Mallett Brian J. Ward |
| author_sort | Karen K. Yam |
| collection | DOAJ |
| description | We investigated the long-term immune profiles of dose-sparing, AS03-adjuvanted vaccines compared to a traditional high-dose, unadjuvated influenza vaccine formulation. BALB/c mice received 2 IM injections of influenza A/Uruguay/716/2007 (H3N2) split vaccine antigen: high-dose (HD) (3 µg hemagglutinin (HA)/dose) or low-dose (LD) formulations (0.03 µg or 0.003 µg HA) with AS03 and were followed to 34 weeks post-boost (pb). We examined serologic responses, spleen and bone marrow (BM) HA-specific antibody-secreting cells (ASCs) by ELISpot, influenza-specific cytokine/chemokine production in re-stimulated splenocytes by multiplex ELISA, and antigen-specific CD4+ T cells that express cytokines (IL-2, IFNγ, TNFα and IL-5) by flow cytometry. All formulations elicited robust serum antibody titers that persisted for at least 34 weeks. The number of antigen-specific ASCs in the spleen and BM were higher in the 2 LD +AS03 groups, but despite having fewer ASCs, the average spot size in the HD-unadjuvanted group was larger at later time-points, suggesting greater antibody production per cell. Striking differences in the long-term profiles induced by the different vaccine formulations may contribute to these different ASC profiles. The HD-unadjuvanted vaccine elicited strong Th2 cytokines during the first 6 weeks pb but LD+AS03 groups generated broader, more durable responses at later timepoints. Finally, the 0.03 µg HA+AS03 group generated the greatest number of antigen-specific CD4+ T cells and the highest percentage of poly-functional cells that expressed 2 or more cytokines. Although all of the tested vaccines induced durable antibody responses, we show that different vaccine formulations (dose-sparing, adjuvant) generate distinct long-term immune profiles. Furthermore, our data suggest that the different profiles may be generated through unique mechanisms. |
| first_indexed | 2024-03-11T22:01:38Z |
| format | Article |
| id | doaj.art-565526ab1d2b49618a14b6cf40a2301e |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:01:38Z |
| publishDate | 2017-03-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-565526ab1d2b49618a14b6cf40a2301e2023-09-25T11:00:54ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2017-03-0113356157110.1080/21645515.2016.12413601241360Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c miceKaren K. Yam0Angela Brewer1Virginie Bleau2Édith Beaulieu3Corey P. Mallett4Brian J. Ward5Research Institute of the McGill University Health CentreResearch Institute of the McGill University Health CentreResearch Institute of the McGill University Health CentreGSK VaccinesGSK VaccinesResearch Institute of the McGill University Health CentreWe investigated the long-term immune profiles of dose-sparing, AS03-adjuvanted vaccines compared to a traditional high-dose, unadjuvated influenza vaccine formulation. BALB/c mice received 2 IM injections of influenza A/Uruguay/716/2007 (H3N2) split vaccine antigen: high-dose (HD) (3 µg hemagglutinin (HA)/dose) or low-dose (LD) formulations (0.03 µg or 0.003 µg HA) with AS03 and were followed to 34 weeks post-boost (pb). We examined serologic responses, spleen and bone marrow (BM) HA-specific antibody-secreting cells (ASCs) by ELISpot, influenza-specific cytokine/chemokine production in re-stimulated splenocytes by multiplex ELISA, and antigen-specific CD4+ T cells that express cytokines (IL-2, IFNγ, TNFα and IL-5) by flow cytometry. All formulations elicited robust serum antibody titers that persisted for at least 34 weeks. The number of antigen-specific ASCs in the spleen and BM were higher in the 2 LD +AS03 groups, but despite having fewer ASCs, the average spot size in the HD-unadjuvanted group was larger at later time-points, suggesting greater antibody production per cell. Striking differences in the long-term profiles induced by the different vaccine formulations may contribute to these different ASC profiles. The HD-unadjuvanted vaccine elicited strong Th2 cytokines during the first 6 weeks pb but LD+AS03 groups generated broader, more durable responses at later timepoints. Finally, the 0.03 µg HA+AS03 group generated the greatest number of antigen-specific CD4+ T cells and the highest percentage of poly-functional cells that expressed 2 or more cytokines. Although all of the tested vaccines induced durable antibody responses, we show that different vaccine formulations (dose-sparing, adjuvant) generate distinct long-term immune profiles. Furthermore, our data suggest that the different profiles may be generated through unique mechanisms.http://dx.doi.org/10.1080/21645515.2016.1241360adjuvantantibody-secreting cellsas03cytokinechemokinedose-sparinghemagglutination inhibitioninfluenzalong-term immune responsemicroneutralizationvaccine |
| spellingShingle | Karen K. Yam Angela Brewer Virginie Bleau Édith Beaulieu Corey P. Mallett Brian J. Ward Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice Human Vaccines & Immunotherapeutics adjuvant antibody-secreting cells as03 cytokine chemokine dose-sparing hemagglutination inhibition influenza long-term immune response microneutralization vaccine |
| title | Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice |
| title_full | Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice |
| title_fullStr | Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice |
| title_full_unstemmed | Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice |
| title_short | Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice |
| title_sort | low hemagglutinin antigen dose influenza vaccines adjuvanted with as03 alter the long term immune responses in balb c mice |
| topic | adjuvant antibody-secreting cells as03 cytokine chemokine dose-sparing hemagglutination inhibition influenza long-term immune response microneutralization vaccine |
| url | http://dx.doi.org/10.1080/21645515.2016.1241360 |
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