Protection Elicited by Attenuated Live <i>Yersinia pestis</i> Vaccine Strains against Lethal Infection with Virulent <i>Y. pestis</i>
The etiologic agent of plague, <i>Yersinia pestis</i>, is a globally distributed pathogen which poses both a natural and adversarial threat. Due largely to the rapid course and high mortality of pneumonic plague, vaccines are greatly needed. Two-component protein vaccines have been unrel...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-02-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/9/2/161 |
| _version_ | 1827589093606817792 |
|---|---|
| author | Christopher K. Cote Sergei S. Biryukov Christopher P. Klimko Jennifer L. Shoe Melissa Hunter Raysa Rosario-Acevedo David P. Fetterer Krishna L. Moody Joshua R. Meyer Nathaniel O. Rill Jennifer L. Dankmeyer Patricia L. Worsham Joel A. Bozue Susan L. Welkos |
| author_facet | Christopher K. Cote Sergei S. Biryukov Christopher P. Klimko Jennifer L. Shoe Melissa Hunter Raysa Rosario-Acevedo David P. Fetterer Krishna L. Moody Joshua R. Meyer Nathaniel O. Rill Jennifer L. Dankmeyer Patricia L. Worsham Joel A. Bozue Susan L. Welkos |
| author_sort | Christopher K. Cote |
| collection | DOAJ |
| description | The etiologic agent of plague, <i>Yersinia pestis</i>, is a globally distributed pathogen which poses both a natural and adversarial threat. Due largely to the rapid course and high mortality of pneumonic plague, vaccines are greatly needed. Two-component protein vaccines have been unreliable and potentially vulnerable to vaccine resistance. We evaluated the safety and efficacy of eight live <i>Y. pestis</i> strains derived from virulent strains CO92 or KIM6+ and mutated in one or more virulence-associated gene(s) or cured of plasmid pPst. Stringent, single-dose vaccination allowed down-selection of the two safest and most protective vaccine candidates, CO92 mutants <i>pgm</i>- pPst- and Δ<i>yscN</i>. Both completely protected BALB/c mice against subcutaneous and aerosol challenge with <i>Y. pestis</i>. Strain CD-1 outbred mice were more resistant to bubonic (but not pneumonic) plague than BALB/c mice, but the vaccines elicited partial protection of CD-1 mice against aerosol challenge, while providing full protection against subcutaneous challenge. A Δ<i>yscN</i> mutant of the nonencapsulated C12 strain was expected to display antigens previously concealed by the capsule. C12 Δ<i>yscN</i> elicited negligible titers to F1 but comparable antibody levels to whole killed bacteria, as did CO92 Δ<i>yscN</i>. Although one dose of C12 Δ<i>yscN</i> was not protective, vaccination with two doses of either CO92 Δ<i>yscN,</i> or a combination of the Δysc<i>N</i> mutants of C12 and CO92, protected optimally against lethal bubonic or pneumonic plague. Protection against encapsulated <i>Y. pestis</i> required inclusion of F1 in the vaccine and was associated with high anti-F1 titers. |
| first_indexed | 2024-03-09T00:49:47Z |
| format | Article |
| id | doaj.art-a25d4d39f1f54a6da9f2ac85559f6d28 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T00:49:47Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-a25d4d39f1f54a6da9f2ac85559f6d282023-12-11T17:19:13ZengMDPI AGVaccines2076-393X2021-02-019216110.3390/vaccines9020161Protection Elicited by Attenuated Live <i>Yersinia pestis</i> Vaccine Strains against Lethal Infection with Virulent <i>Y. pestis</i>Christopher K. Cote0Sergei S. Biryukov1Christopher P. Klimko2Jennifer L. Shoe3Melissa Hunter4Raysa Rosario-Acevedo5David P. Fetterer6Krishna L. Moody7Joshua R. Meyer8Nathaniel O. Rill9Jennifer L. Dankmeyer10Patricia L. Worsham11Joel A. Bozue12Susan L. Welkos13Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USABacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USAThe etiologic agent of plague, <i>Yersinia pestis</i>, is a globally distributed pathogen which poses both a natural and adversarial threat. Due largely to the rapid course and high mortality of pneumonic plague, vaccines are greatly needed. Two-component protein vaccines have been unreliable and potentially vulnerable to vaccine resistance. We evaluated the safety and efficacy of eight live <i>Y. pestis</i> strains derived from virulent strains CO92 or KIM6+ and mutated in one or more virulence-associated gene(s) or cured of plasmid pPst. Stringent, single-dose vaccination allowed down-selection of the two safest and most protective vaccine candidates, CO92 mutants <i>pgm</i>- pPst- and Δ<i>yscN</i>. Both completely protected BALB/c mice against subcutaneous and aerosol challenge with <i>Y. pestis</i>. Strain CD-1 outbred mice were more resistant to bubonic (but not pneumonic) plague than BALB/c mice, but the vaccines elicited partial protection of CD-1 mice against aerosol challenge, while providing full protection against subcutaneous challenge. A Δ<i>yscN</i> mutant of the nonencapsulated C12 strain was expected to display antigens previously concealed by the capsule. C12 Δ<i>yscN</i> elicited negligible titers to F1 but comparable antibody levels to whole killed bacteria, as did CO92 Δ<i>yscN</i>. Although one dose of C12 Δ<i>yscN</i> was not protective, vaccination with two doses of either CO92 Δ<i>yscN,</i> or a combination of the Δysc<i>N</i> mutants of C12 and CO92, protected optimally against lethal bubonic or pneumonic plague. Protection against encapsulated <i>Y. pestis</i> required inclusion of F1 in the vaccine and was associated with high anti-F1 titers.https://www.mdpi.com/2076-393X/9/2/161plague<i>Yersinia pestis</i>vaccinemicebubonicpneumonic |
| spellingShingle | Christopher K. Cote Sergei S. Biryukov Christopher P. Klimko Jennifer L. Shoe Melissa Hunter Raysa Rosario-Acevedo David P. Fetterer Krishna L. Moody Joshua R. Meyer Nathaniel O. Rill Jennifer L. Dankmeyer Patricia L. Worsham Joel A. Bozue Susan L. Welkos Protection Elicited by Attenuated Live <i>Yersinia pestis</i> Vaccine Strains against Lethal Infection with Virulent <i>Y. pestis</i> Vaccines plague <i>Yersinia pestis</i> vaccine mice bubonic pneumonic |
| title | Protection Elicited by Attenuated Live <i>Yersinia pestis</i> Vaccine Strains against Lethal Infection with Virulent <i>Y. pestis</i> |
| title_full | Protection Elicited by Attenuated Live <i>Yersinia pestis</i> Vaccine Strains against Lethal Infection with Virulent <i>Y. pestis</i> |
| title_fullStr | Protection Elicited by Attenuated Live <i>Yersinia pestis</i> Vaccine Strains against Lethal Infection with Virulent <i>Y. pestis</i> |
| title_full_unstemmed | Protection Elicited by Attenuated Live <i>Yersinia pestis</i> Vaccine Strains against Lethal Infection with Virulent <i>Y. pestis</i> |
| title_short | Protection Elicited by Attenuated Live <i>Yersinia pestis</i> Vaccine Strains against Lethal Infection with Virulent <i>Y. pestis</i> |
| title_sort | protection elicited by attenuated live i yersinia pestis i vaccine strains against lethal infection with virulent i y pestis i |
| topic | plague <i>Yersinia pestis</i> vaccine mice bubonic pneumonic |
| url | https://www.mdpi.com/2076-393X/9/2/161 |
| work_keys_str_mv | AT christopherkcote protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi AT sergeisbiryukov protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi AT christopherpklimko protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi AT jenniferlshoe protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi AT melissahunter protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi AT raysarosarioacevedo protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi AT davidpfetterer protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi AT krishnalmoody protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi AT joshuarmeyer protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi AT nathanielorill protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi AT jenniferldankmeyer protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi AT patricialworsham protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi AT joelabozue protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi AT susanlwelkos protectionelicitedbyattenuatedliveiyersiniapestisivaccinestrainsagainstlethalinfectionwithvirulentiypestisi |