Novel antibody competition binding assay identifies distinct serological profiles associated with protection
IntroductionPre-erythrocytic malaria vaccines hold the promise of inducing sterile protection thereby preventing the morbidity and mortality associated with Plasmodium infection. The main surface antigen of P. falciparum sporozoites, i.e., the circumsporozoite protein (CSP), has been extensively exp...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-12-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1303446/full |
| _version_ | 1827589678998487040 |
|---|---|
| author | Jessica S. Bolton Randall S. MacGill Emily Locke Jason A. Regules Elke S. Bergmann-Leitner |
| author_facet | Jessica S. Bolton Randall S. MacGill Emily Locke Jason A. Regules Elke S. Bergmann-Leitner |
| author_sort | Jessica S. Bolton |
| collection | DOAJ |
| description | IntroductionPre-erythrocytic malaria vaccines hold the promise of inducing sterile protection thereby preventing the morbidity and mortality associated with Plasmodium infection. The main surface antigen of P. falciparum sporozoites, i.e., the circumsporozoite protein (CSP), has been extensively explored as a target of such vaccines with significant success in recent years. Systematic adjuvant selection, refinements of the immunization regimen, and physical properties of the antigen may all contribute to the potential of increasing the efficacy of CSP-based vaccines. Protection appears to be dependent in large part on CSP antibodies. However due to a knowledge gap related to the exact correlates of immunity, there is a critical need to improve our ability to down select candidates preclinically before entering clinical trials including with controlled human malaria infections (CHMI).MethodsWe developed a novel multiplex competition assay based on well-characterized monoclonal antibodies (mAbs) that target crucial epitopes across the CSP molecule. This new tool assesses both, quality and epitope-specific concentrations of vaccine-induced antibodies by measuring their equivalency with a panel of well-characterized, CSP-epitope-specific mAbs.ResultsApplying this method to RTS,S-immune sera from a CHMI trial demonstrated a quantitative epitope-specificity profile of antibody responses that can differentiate between protected vs. nonprotected individuals. Aligning vaccine efficacy with quantitation of the epitope fine specificity results of this equivalency assay reveals the importance of epitope specificity.DiscussionThe newly developed serological equivalence assay will inform future vaccine design and possibly even adjuvant selection. This methodology can be adapted to other antigens and disease models, when a panel of relevant mAbs exists, and could offer a unique tool for comparing and down-selecting vaccine formulations. |
| first_indexed | 2024-03-09T01:05:21Z |
| format | Article |
| id | doaj.art-0ade5144f61c4c5a99b1bb4130173d62 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-09T01:05:21Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0ade5144f61c4c5a99b1bb4130173d622023-12-11T09:50:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.13034461303446Novel antibody competition binding assay identifies distinct serological profiles associated with protectionJessica S. Bolton0Randall S. MacGill1Emily Locke2Jason A. Regules3Elke S. Bergmann-Leitner4Biologics Research & Development, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, United StatesCenter for Vaccine Innovation and Access, PATH, Washington, DC, United StatesCenter for Vaccine Innovation and Access, PATH, Washington, DC, United StatesBiologics Research & Development, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, United StatesBiologics Research & Development, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD, United StatesIntroductionPre-erythrocytic malaria vaccines hold the promise of inducing sterile protection thereby preventing the morbidity and mortality associated with Plasmodium infection. The main surface antigen of P. falciparum sporozoites, i.e., the circumsporozoite protein (CSP), has been extensively explored as a target of such vaccines with significant success in recent years. Systematic adjuvant selection, refinements of the immunization regimen, and physical properties of the antigen may all contribute to the potential of increasing the efficacy of CSP-based vaccines. Protection appears to be dependent in large part on CSP antibodies. However due to a knowledge gap related to the exact correlates of immunity, there is a critical need to improve our ability to down select candidates preclinically before entering clinical trials including with controlled human malaria infections (CHMI).MethodsWe developed a novel multiplex competition assay based on well-characterized monoclonal antibodies (mAbs) that target crucial epitopes across the CSP molecule. This new tool assesses both, quality and epitope-specific concentrations of vaccine-induced antibodies by measuring their equivalency with a panel of well-characterized, CSP-epitope-specific mAbs.ResultsApplying this method to RTS,S-immune sera from a CHMI trial demonstrated a quantitative epitope-specificity profile of antibody responses that can differentiate between protected vs. nonprotected individuals. Aligning vaccine efficacy with quantitation of the epitope fine specificity results of this equivalency assay reveals the importance of epitope specificity.DiscussionThe newly developed serological equivalence assay will inform future vaccine design and possibly even adjuvant selection. This methodology can be adapted to other antigens and disease models, when a panel of relevant mAbs exists, and could offer a unique tool for comparing and down-selecting vaccine formulations.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1303446/fullserologycircumsporozoite proteinantigen-specificityequivalencyvaccineprotection |
| spellingShingle | Jessica S. Bolton Randall S. MacGill Emily Locke Jason A. Regules Elke S. Bergmann-Leitner Novel antibody competition binding assay identifies distinct serological profiles associated with protection Frontiers in Immunology serology circumsporozoite protein antigen-specificity equivalency vaccine protection |
| title | Novel antibody competition binding assay identifies distinct serological profiles associated with protection |
| title_full | Novel antibody competition binding assay identifies distinct serological profiles associated with protection |
| title_fullStr | Novel antibody competition binding assay identifies distinct serological profiles associated with protection |
| title_full_unstemmed | Novel antibody competition binding assay identifies distinct serological profiles associated with protection |
| title_short | Novel antibody competition binding assay identifies distinct serological profiles associated with protection |
| title_sort | novel antibody competition binding assay identifies distinct serological profiles associated with protection |
| topic | serology circumsporozoite protein antigen-specificity equivalency vaccine protection |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1303446/full |
| work_keys_str_mv | AT jessicasbolton novelantibodycompetitionbindingassayidentifiesdistinctserologicalprofilesassociatedwithprotection AT randallsmacgill novelantibodycompetitionbindingassayidentifiesdistinctserologicalprofilesassociatedwithprotection AT emilylocke novelantibodycompetitionbindingassayidentifiesdistinctserologicalprofilesassociatedwithprotection AT jasonaregules novelantibodycompetitionbindingassayidentifiesdistinctserologicalprofilesassociatedwithprotection AT elkesbergmannleitner novelantibodycompetitionbindingassayidentifiesdistinctserologicalprofilesassociatedwithprotection |