Predictors of Survival after Vaccination in a Pneumonic Plague Model
<b>Background:</b> The need for an updated plague vaccine is highlighted by outbreaks in endemic regions together with the pandemic potential of this disease. There is no easily available, approved vaccine. <b>Methods:</b> Here we have used a murine model of pneumonic plague...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/2/145 |
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| author | Barry D. Moore Clair Macleod Lisa Henning Robert Krile Ying-Liang Chou Thomas R. Laws Wendy A. Butcher Kristoffer M. Moore Nicola J. Walker Ethel Diane Williamson Darrell R. Galloway |
| author_facet | Barry D. Moore Clair Macleod Lisa Henning Robert Krile Ying-Liang Chou Thomas R. Laws Wendy A. Butcher Kristoffer M. Moore Nicola J. Walker Ethel Diane Williamson Darrell R. Galloway |
| author_sort | Barry D. Moore |
| collection | DOAJ |
| description | <b>Background:</b> The need for an updated plague vaccine is highlighted by outbreaks in endemic regions together with the pandemic potential of this disease. There is no easily available, approved vaccine. <b>Methods:</b> Here we have used a murine model of pneumonic plague to examine the factors that maximise immunogenicity and contribute to survival following vaccination. We varied vaccine type, as either a genetic fusion of the F1 and V protein antigens or a mixture of these two recombinant antigens, as well as antigen dose-level and formulation in order to correlate immune response to survival. <b>Results:</b> Whilst there was interaction between each of the variables of vaccine type, dose level and formulation and these all contributed to survival, vaccine formulation in protein-coated microcrystals (PCMCs) was the key contributor in inducing antibody titres. From these data, we propose a cut-off in total serum antibody titre to the F1 and V proteins of 100 µg/mL and 200 µg/mL, respectively. At these thresholds, survival is predicted in this murine pneumonic model to be >90%. Within the total titre of antibody to the V antigen, the neutralising antibody component correlated with dose level and was enhanced when the V antigen in free form was formulated in PCMCs. Antibody titre to F1 was limited by fusion to V, but this was compensated for by PCMC formulation. <b>Conclusions:</b> These data will enable clinical assessment of this and other candidate plague vaccines that utilise the same vaccine antigens by identifying a target antibody titre from murine models, which will guide the evaluation of clinical titres as serological surrogate markers of efficacy. |
| first_indexed | 2024-03-09T20:54:54Z |
| format | Article |
| id | doaj.art-d5730a07d23a4f4b930a89a083d222fe |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T20:54:54Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-d5730a07d23a4f4b930a89a083d222fe2023-11-23T22:24:15ZengMDPI AGVaccines2076-393X2022-01-0110214510.3390/vaccines10020145Predictors of Survival after Vaccination in a Pneumonic Plague ModelBarry D. Moore0Clair Macleod1Lisa Henning2Robert Krile3Ying-Liang Chou4Thomas R. Laws5Wendy A. Butcher6Kristoffer M. Moore7Nicola J. Walker8Ethel Diane Williamson9Darrell R. Galloway10Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XQ, UKDepartment of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XQ, UKBattelle Biomedical Research Center, West Jefferson, OH 43162, USABattelle Biomedical Research Center, West Jefferson, OH 43162, USABattelle Biomedical Research Center, West Jefferson, OH 43162, USACBR Division, Dstl Porton Down, Salisbury SP4 0JQ, UKCBR Division, Dstl Porton Down, Salisbury SP4 0JQ, UKCBR Division, Dstl Porton Down, Salisbury SP4 0JQ, UKCBR Division, Dstl Porton Down, Salisbury SP4 0JQ, UKCBR Division, Dstl Porton Down, Salisbury SP4 0JQ, UKDepartment of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA<b>Background:</b> The need for an updated plague vaccine is highlighted by outbreaks in endemic regions together with the pandemic potential of this disease. There is no easily available, approved vaccine. <b>Methods:</b> Here we have used a murine model of pneumonic plague to examine the factors that maximise immunogenicity and contribute to survival following vaccination. We varied vaccine type, as either a genetic fusion of the F1 and V protein antigens or a mixture of these two recombinant antigens, as well as antigen dose-level and formulation in order to correlate immune response to survival. <b>Results:</b> Whilst there was interaction between each of the variables of vaccine type, dose level and formulation and these all contributed to survival, vaccine formulation in protein-coated microcrystals (PCMCs) was the key contributor in inducing antibody titres. From these data, we propose a cut-off in total serum antibody titre to the F1 and V proteins of 100 µg/mL and 200 µg/mL, respectively. At these thresholds, survival is predicted in this murine pneumonic model to be >90%. Within the total titre of antibody to the V antigen, the neutralising antibody component correlated with dose level and was enhanced when the V antigen in free form was formulated in PCMCs. Antibody titre to F1 was limited by fusion to V, but this was compensated for by PCMC formulation. <b>Conclusions:</b> These data will enable clinical assessment of this and other candidate plague vaccines that utilise the same vaccine antigens by identifying a target antibody titre from murine models, which will guide the evaluation of clinical titres as serological surrogate markers of efficacy.https://www.mdpi.com/2076-393X/10/2/145plaguevaccineformulationimmunitycorrelates |
| spellingShingle | Barry D. Moore Clair Macleod Lisa Henning Robert Krile Ying-Liang Chou Thomas R. Laws Wendy A. Butcher Kristoffer M. Moore Nicola J. Walker Ethel Diane Williamson Darrell R. Galloway Predictors of Survival after Vaccination in a Pneumonic Plague Model Vaccines plague vaccine formulation immunity correlates |
| title | Predictors of Survival after Vaccination in a Pneumonic Plague Model |
| title_full | Predictors of Survival after Vaccination in a Pneumonic Plague Model |
| title_fullStr | Predictors of Survival after Vaccination in a Pneumonic Plague Model |
| title_full_unstemmed | Predictors of Survival after Vaccination in a Pneumonic Plague Model |
| title_short | Predictors of Survival after Vaccination in a Pneumonic Plague Model |
| title_sort | predictors of survival after vaccination in a pneumonic plague model |
| topic | plague vaccine formulation immunity correlates |
| url | https://www.mdpi.com/2076-393X/10/2/145 |
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