LigA formulated in AS04 or Montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosis
Leptospirosis is a zoonotic disease of global importance. The current vaccine provides serovar-specific and short-term immunity and does not prevent bacterial shedding in infected animals. Subunit vaccines based on surface proteins have shown to induce protection in an animal model. However, these p...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.985802/full |
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| author | Vivek P. Varma Vivek P. Varma Mohammad Kadivella Mohammad Kadivella Ajay Kumar Ajay Kumar Sridhar Kavela Syed M. Faisal Syed M. Faisal |
| author_facet | Vivek P. Varma Vivek P. Varma Mohammad Kadivella Mohammad Kadivella Ajay Kumar Ajay Kumar Sridhar Kavela Syed M. Faisal Syed M. Faisal |
| author_sort | Vivek P. Varma |
| collection | DOAJ |
| description | Leptospirosis is a zoonotic disease of global importance. The current vaccine provides serovar-specific and short-term immunity and does not prevent bacterial shedding in infected animals. Subunit vaccines based on surface proteins have shown to induce protection in an animal model. However, these proteins were tested with non-clinical adjuvants and induced low to moderate protective efficacy. We formulated a variable region of Leptospira immunoglobulin-like protein A (LAV) in clinical adjuvants, AS04 and Montanide ISA720VG, and then evaluated the immune response in mice and protective efficacy in a hamster model. Our results show that animals immunized with LAV-AS04 and LAV-Montanide ISA720VG (LAV-M) induced significantly higher levels of LAV-specific antibodies than LAV-Alum. While LAV-Alum induced Th2 response with the induction of IgG1 and IL-4, AS04 and LAV-M induced a mixed Th1/Th2 response with significant levels of both IgG1/IL-4 and IgG2c/IFN-γ. Both LAV-AS04 and LAV-M induced the generation of a significantly higher number of cytotoxic T cells (CTLs). The immune response in LAV-AS04- and LAV-M-immunized animals was maintained for a long period (>180 days) with the generation of a significant level of B- and T-cell memory. The strong immune response by both vaccines correlated to enhanced recruitment and activation of innate immune cells particularly DCs at draining lymph nodes and the formation of germinal centers (GCs). Furthermore, the immune response generated in mice correlated to protective efficacy in the hamster model of leptospirosis. These results indicate that LAV-AS04 and LAV-M are promising vaccines and can be further evaluated in clinical trials. |
| first_indexed | 2024-04-11T17:04:21Z |
| format | Article |
| id | doaj.art-0ab1a7da882041ffb0641d11d65eae73 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T17:04:21Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0ab1a7da882041ffb0641d11d65eae732022-12-22T04:13:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.985802985802LigA formulated in AS04 or Montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosisVivek P. Varma0Vivek P. Varma1Mohammad Kadivella2Mohammad Kadivella3Ajay Kumar4Ajay Kumar5Sridhar Kavela6Syed M. Faisal7Syed M. Faisal8Laboratory of Vaccine Immunology, National Institute of Animal Biotechnology, Hyderabad, IndiaGraduate Studies, Manipal Academy of Higher Education, Manipal, Karnataka, IndiaLaboratory of Vaccine Immunology, National Institute of Animal Biotechnology, Hyderabad, IndiaRegional Centre for Biotechnology, Faridabad, IndiaLaboratory of Vaccine Immunology, National Institute of Animal Biotechnology, Hyderabad, IndiaRegional Centre for Biotechnology, Faridabad, IndiaLaboratory of Vaccine Immunology, National Institute of Animal Biotechnology, Hyderabad, IndiaLaboratory of Vaccine Immunology, National Institute of Animal Biotechnology, Hyderabad, IndiaRegional Centre for Biotechnology, Faridabad, IndiaLeptospirosis is a zoonotic disease of global importance. The current vaccine provides serovar-specific and short-term immunity and does not prevent bacterial shedding in infected animals. Subunit vaccines based on surface proteins have shown to induce protection in an animal model. However, these proteins were tested with non-clinical adjuvants and induced low to moderate protective efficacy. We formulated a variable region of Leptospira immunoglobulin-like protein A (LAV) in clinical adjuvants, AS04 and Montanide ISA720VG, and then evaluated the immune response in mice and protective efficacy in a hamster model. Our results show that animals immunized with LAV-AS04 and LAV-Montanide ISA720VG (LAV-M) induced significantly higher levels of LAV-specific antibodies than LAV-Alum. While LAV-Alum induced Th2 response with the induction of IgG1 and IL-4, AS04 and LAV-M induced a mixed Th1/Th2 response with significant levels of both IgG1/IL-4 and IgG2c/IFN-γ. Both LAV-AS04 and LAV-M induced the generation of a significantly higher number of cytotoxic T cells (CTLs). The immune response in LAV-AS04- and LAV-M-immunized animals was maintained for a long period (>180 days) with the generation of a significant level of B- and T-cell memory. The strong immune response by both vaccines correlated to enhanced recruitment and activation of innate immune cells particularly DCs at draining lymph nodes and the formation of germinal centers (GCs). Furthermore, the immune response generated in mice correlated to protective efficacy in the hamster model of leptospirosis. These results indicate that LAV-AS04 and LAV-M are promising vaccines and can be further evaluated in clinical trials.https://www.frontiersin.org/articles/10.3389/fimmu.2022.985802/fullLIGAclinical adjuvantvaccineAS04Montanide ISA720VGleptospirosis |
| spellingShingle | Vivek P. Varma Vivek P. Varma Mohammad Kadivella Mohammad Kadivella Ajay Kumar Ajay Kumar Sridhar Kavela Syed M. Faisal Syed M. Faisal LigA formulated in AS04 or Montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosis Frontiers in Immunology LIGA clinical adjuvant vaccine AS04 Montanide ISA720VG leptospirosis |
| title | LigA formulated in AS04 or Montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosis |
| title_full | LigA formulated in AS04 or Montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosis |
| title_fullStr | LigA formulated in AS04 or Montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosis |
| title_full_unstemmed | LigA formulated in AS04 or Montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosis |
| title_short | LigA formulated in AS04 or Montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosis |
| title_sort | liga formulated in as04 or montanide isa720vg induced superior immune response compared to alum which correlated to protective efficacy in a hamster model of leptospirosis |
| topic | LIGA clinical adjuvant vaccine AS04 Montanide ISA720VG leptospirosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.985802/full |
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