Binding Sites of Anti-Lcr V Monoclonal Antibodies Are More Critical than the Avidities and Affinities for Passive Protection against <i>Yersinia pestis</i> Infection in a Bubonic Plague Model
Plague is a zoonotic disease that is caused by <i>Yersinia pestis</i>. Monoclonal antibodies (mAbs) that bind to the V-antigen, a virulence factor that is produced by <i>Y. pestis</i>, can passively protect mice from plague. An analysis of protective mAbs that bind to V-antig...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-08-01
|
| Series: | Antibodies |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4468/9/3/37 |
| _version_ | 1797560469137915904 |
|---|---|
| author | Kei Amemiya Jennifer L. Dankmeyer Sarah L. Keasey Sylvia R. Trevino Michael M. Wormald Stephanie A. Halasohoris Wilson J. Ribot David P. Fetterer Christopher K. Cote Patricia L. Worsham Jeffrey J. Adamovicz Robert G. Ulrich |
| author_facet | Kei Amemiya Jennifer L. Dankmeyer Sarah L. Keasey Sylvia R. Trevino Michael M. Wormald Stephanie A. Halasohoris Wilson J. Ribot David P. Fetterer Christopher K. Cote Patricia L. Worsham Jeffrey J. Adamovicz Robert G. Ulrich |
| author_sort | Kei Amemiya |
| collection | DOAJ |
| description | Plague is a zoonotic disease that is caused by <i>Yersinia pestis</i>. Monoclonal antibodies (mAbs) that bind to the V-antigen, a virulence factor that is produced by <i>Y. pestis</i>, can passively protect mice from plague. An analysis of protective mAbs that bind to V-antigen was made to assess binding sites, avidities, and affinities. Anti-V mAbs were screened for their efficacy in a murine model of plague. Antigen-binding sites of protective V mAbs were determined with a linear peptide library, V-antigen fragment, competitive binding, and surface plasmon resonance. The avidities to the V-antigen was determined by ELISA, and affinities of the mAbs to the V-antigen were determined by surface plasmon resonance. The most protective mAb 7.3 bound to a unique conformational site on the V-antigen, while a less protective mAb bound to a different conformational site located on the same V-antigen fragment as mAb 7.3. The avidity of mAb 7.3 for the V-antigen was neither the strongest overall nor did it have the highest affinity for the V-antigen. The binding site of the most protective mAb was critical in its ability to protect against a lethal plague challenge. |
| first_indexed | 2024-03-10T18:00:59Z |
| format | Article |
| id | doaj.art-673628452d76476886124e3319433074 |
| institution | Directory Open Access Journal |
| issn | 2073-4468 |
| language | English |
| last_indexed | 2024-03-10T18:00:59Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibodies |
| spelling | doaj.art-673628452d76476886124e33194330742023-11-20T08:52:33ZengMDPI AGAntibodies2073-44682020-08-01933710.3390/antib9030037Binding Sites of Anti-Lcr V Monoclonal Antibodies Are More Critical than the Avidities and Affinities for Passive Protection against <i>Yersinia pestis</i> Infection in a Bubonic Plague ModelKei Amemiya0Jennifer L. Dankmeyer1Sarah L. Keasey2Sylvia R. Trevino3Michael M. Wormald4Stephanie A. Halasohoris5Wilson J. Ribot6David P. Fetterer7Christopher K. Cote8Patricia L. Worsham9Jeffrey J. Adamovicz10Robert G. Ulrich11Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USAMolecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USAMolecular and Translational Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USAPlague is a zoonotic disease that is caused by <i>Yersinia pestis</i>. Monoclonal antibodies (mAbs) that bind to the V-antigen, a virulence factor that is produced by <i>Y. pestis</i>, can passively protect mice from plague. An analysis of protective mAbs that bind to V-antigen was made to assess binding sites, avidities, and affinities. Anti-V mAbs were screened for their efficacy in a murine model of plague. Antigen-binding sites of protective V mAbs were determined with a linear peptide library, V-antigen fragment, competitive binding, and surface plasmon resonance. The avidities to the V-antigen was determined by ELISA, and affinities of the mAbs to the V-antigen were determined by surface plasmon resonance. The most protective mAb 7.3 bound to a unique conformational site on the V-antigen, while a less protective mAb bound to a different conformational site located on the same V-antigen fragment as mAb 7.3. The avidity of mAb 7.3 for the V-antigen was neither the strongest overall nor did it have the highest affinity for the V-antigen. The binding site of the most protective mAb was critical in its ability to protect against a lethal plague challenge.https://www.mdpi.com/2073-4468/9/3/37monoclonal antibodies<i>Yersinia pestis</i>plaguebinding sitesaviditiesaffinities |
| spellingShingle | Kei Amemiya Jennifer L. Dankmeyer Sarah L. Keasey Sylvia R. Trevino Michael M. Wormald Stephanie A. Halasohoris Wilson J. Ribot David P. Fetterer Christopher K. Cote Patricia L. Worsham Jeffrey J. Adamovicz Robert G. Ulrich Binding Sites of Anti-Lcr V Monoclonal Antibodies Are More Critical than the Avidities and Affinities for Passive Protection against <i>Yersinia pestis</i> Infection in a Bubonic Plague Model Antibodies monoclonal antibodies <i>Yersinia pestis</i> plague binding sites avidities affinities |
| title | Binding Sites of Anti-Lcr V Monoclonal Antibodies Are More Critical than the Avidities and Affinities for Passive Protection against <i>Yersinia pestis</i> Infection in a Bubonic Plague Model |
| title_full | Binding Sites of Anti-Lcr V Monoclonal Antibodies Are More Critical than the Avidities and Affinities for Passive Protection against <i>Yersinia pestis</i> Infection in a Bubonic Plague Model |
| title_fullStr | Binding Sites of Anti-Lcr V Monoclonal Antibodies Are More Critical than the Avidities and Affinities for Passive Protection against <i>Yersinia pestis</i> Infection in a Bubonic Plague Model |
| title_full_unstemmed | Binding Sites of Anti-Lcr V Monoclonal Antibodies Are More Critical than the Avidities and Affinities for Passive Protection against <i>Yersinia pestis</i> Infection in a Bubonic Plague Model |
| title_short | Binding Sites of Anti-Lcr V Monoclonal Antibodies Are More Critical than the Avidities and Affinities for Passive Protection against <i>Yersinia pestis</i> Infection in a Bubonic Plague Model |
| title_sort | binding sites of anti lcr v monoclonal antibodies are more critical than the avidities and affinities for passive protection against i yersinia pestis i infection in a bubonic plague model |
| topic | monoclonal antibodies <i>Yersinia pestis</i> plague binding sites avidities affinities |
| url | https://www.mdpi.com/2073-4468/9/3/37 |
| work_keys_str_mv | AT keiamemiya bindingsitesofantilcrvmonoclonalantibodiesaremorecriticalthantheaviditiesandaffinitiesforpassiveprotectionagainstiyersiniapestisiinfectioninabubonicplaguemodel AT jenniferldankmeyer bindingsitesofantilcrvmonoclonalantibodiesaremorecriticalthantheaviditiesandaffinitiesforpassiveprotectionagainstiyersiniapestisiinfectioninabubonicplaguemodel AT sarahlkeasey bindingsitesofantilcrvmonoclonalantibodiesaremorecriticalthantheaviditiesandaffinitiesforpassiveprotectionagainstiyersiniapestisiinfectioninabubonicplaguemodel AT sylviartrevino bindingsitesofantilcrvmonoclonalantibodiesaremorecriticalthantheaviditiesandaffinitiesforpassiveprotectionagainstiyersiniapestisiinfectioninabubonicplaguemodel AT michaelmwormald bindingsitesofantilcrvmonoclonalantibodiesaremorecriticalthantheaviditiesandaffinitiesforpassiveprotectionagainstiyersiniapestisiinfectioninabubonicplaguemodel AT stephanieahalasohoris bindingsitesofantilcrvmonoclonalantibodiesaremorecriticalthantheaviditiesandaffinitiesforpassiveprotectionagainstiyersiniapestisiinfectioninabubonicplaguemodel AT wilsonjribot bindingsitesofantilcrvmonoclonalantibodiesaremorecriticalthantheaviditiesandaffinitiesforpassiveprotectionagainstiyersiniapestisiinfectioninabubonicplaguemodel AT davidpfetterer bindingsitesofantilcrvmonoclonalantibodiesaremorecriticalthantheaviditiesandaffinitiesforpassiveprotectionagainstiyersiniapestisiinfectioninabubonicplaguemodel AT christopherkcote bindingsitesofantilcrvmonoclonalantibodiesaremorecriticalthantheaviditiesandaffinitiesforpassiveprotectionagainstiyersiniapestisiinfectioninabubonicplaguemodel AT patricialworsham bindingsitesofantilcrvmonoclonalantibodiesaremorecriticalthantheaviditiesandaffinitiesforpassiveprotectionagainstiyersiniapestisiinfectioninabubonicplaguemodel AT jeffreyjadamovicz bindingsitesofantilcrvmonoclonalantibodiesaremorecriticalthantheaviditiesandaffinitiesforpassiveprotectionagainstiyersiniapestisiinfectioninabubonicplaguemodel AT robertgulrich bindingsitesofantilcrvmonoclonalantibodiesaremorecriticalthantheaviditiesandaffinitiesforpassiveprotectionagainstiyersiniapestisiinfectioninabubonicplaguemodel |