Safety Toxicology Study of Reassortant Mopeia–Lassa Vaccine in Guinea Pigs
(1) Background: Mopeia–Lassa reassortant ML29 virus is an investigational, reassortant virus vaccine for the prevention of Lassa fever caused by Lassa virus (LASV). (2) Methods: The vaccine virus ML29-SF was prepared in Vero cells using a serum-free culture medium under Good Manufacturing Practice....
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MDPI AG
2025-05-01
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| Series: | Future Pharmacology |
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| Online Access: | https://www.mdpi.com/2673-9879/5/2/26 |
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| author | Bradley S. Wahle Peter Pushko Katie Albanese Dylan M. Johnson Irina Tretyakova Igor S. Lukashevich Thomas Rudge |
| author_facet | Bradley S. Wahle Peter Pushko Katie Albanese Dylan M. Johnson Irina Tretyakova Igor S. Lukashevich Thomas Rudge |
| author_sort | Bradley S. Wahle |
| collection | DOAJ |
| description | (1) Background: Mopeia–Lassa reassortant ML29 virus is an investigational, reassortant virus vaccine for the prevention of Lassa fever caused by Lassa virus (LASV). (2) Methods: The vaccine virus ML29-SF was prepared in Vero cells using a serum-free culture medium under Good Manufacturing Practice. A 2-week repeat dose toxicity study was performed in guinea pigs under Good Laboratory Practice (GLP) regulations to assess the local and systemic toxicological effects. (3) Results: Following an intramuscular (IM) or subcutaneous (SC) injection of 10<sup>4</sup> PFU of ML29-SF LASV vaccine at the start of the study, with a second dose 15 days later, no toxicological response attributable to the vaccine was observed. Vaccine-related effects were not observed in any in-life or post-mortem parameter evaluated, including clinical observations, injection site observations, body temperature, body weight, food consumption, ophthalmology, immunology, hematology, clinical chemistry, gross anatomical pathology, organ weights, and histopathology. An immunogenic response, as measured by the elicitation of IgG antibodies against major LASV immunogens, nucleocapsid and glycoprotein precursor, was observed in all vaccine-treated animals prior to the booster dose (Study Day 15) which endured through the end of the study (Study Day 42). There was no evidence of viral shedding in any vaccinated animal. (4) Conclusions: Overall, this single-dose vaccine was locally and systemically well tolerated even after a two-dose repeat administration, confirming the high level of safety of ML29-SF vaccination and supporting the future evaluation of this LASV vaccine, including in clinical trials. |
| format | Article |
| id | doaj-art-a99e665bb1524208ab084cd6d8d8deb3 |
| institution | OA Journals |
| issn | 2673-9879 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Future Pharmacology |
| spelling | doaj-art-a99e665bb1524208ab084cd6d8d8deb32025-08-20T02:21:09ZengMDPI AGFuture Pharmacology2673-98792025-05-01522610.3390/futurepharmacol5020026Safety Toxicology Study of Reassortant Mopeia–Lassa Vaccine in Guinea PigsBradley S. Wahle0Peter Pushko1Katie Albanese2Dylan M. Johnson3Irina Tretyakova4Igor S. Lukashevich5Thomas Rudge6MRIGlobal, Kansas City, MO 64110, USAMedigen, Inc., Frederick, MD 21701, USABattelle, West Jefferson, OH 43162, USASandia National Laboratory, Department of Biotechnology & Bioengineering, Livermore, CA 94550, USAMedigen, Inc., Frederick, MD 21701, USADepartment of Pharmacology and Toxicology, Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40292, USABattelle, West Jefferson, OH 43162, USA(1) Background: Mopeia–Lassa reassortant ML29 virus is an investigational, reassortant virus vaccine for the prevention of Lassa fever caused by Lassa virus (LASV). (2) Methods: The vaccine virus ML29-SF was prepared in Vero cells using a serum-free culture medium under Good Manufacturing Practice. A 2-week repeat dose toxicity study was performed in guinea pigs under Good Laboratory Practice (GLP) regulations to assess the local and systemic toxicological effects. (3) Results: Following an intramuscular (IM) or subcutaneous (SC) injection of 10<sup>4</sup> PFU of ML29-SF LASV vaccine at the start of the study, with a second dose 15 days later, no toxicological response attributable to the vaccine was observed. Vaccine-related effects were not observed in any in-life or post-mortem parameter evaluated, including clinical observations, injection site observations, body temperature, body weight, food consumption, ophthalmology, immunology, hematology, clinical chemistry, gross anatomical pathology, organ weights, and histopathology. An immunogenic response, as measured by the elicitation of IgG antibodies against major LASV immunogens, nucleocapsid and glycoprotein precursor, was observed in all vaccine-treated animals prior to the booster dose (Study Day 15) which endured through the end of the study (Study Day 42). There was no evidence of viral shedding in any vaccinated animal. (4) Conclusions: Overall, this single-dose vaccine was locally and systemically well tolerated even after a two-dose repeat administration, confirming the high level of safety of ML29-SF vaccination and supporting the future evaluation of this LASV vaccine, including in clinical trials.https://www.mdpi.com/2673-9879/5/2/26toxicologyGLPLassavaccinereassortantvirus |
| spellingShingle | Bradley S. Wahle Peter Pushko Katie Albanese Dylan M. Johnson Irina Tretyakova Igor S. Lukashevich Thomas Rudge Safety Toxicology Study of Reassortant Mopeia–Lassa Vaccine in Guinea Pigs Future Pharmacology toxicology GLP Lassa vaccine reassortant virus |
| title | Safety Toxicology Study of Reassortant Mopeia–Lassa Vaccine in Guinea Pigs |
| title_full | Safety Toxicology Study of Reassortant Mopeia–Lassa Vaccine in Guinea Pigs |
| title_fullStr | Safety Toxicology Study of Reassortant Mopeia–Lassa Vaccine in Guinea Pigs |
| title_full_unstemmed | Safety Toxicology Study of Reassortant Mopeia–Lassa Vaccine in Guinea Pigs |
| title_short | Safety Toxicology Study of Reassortant Mopeia–Lassa Vaccine in Guinea Pigs |
| title_sort | safety toxicology study of reassortant mopeia lassa vaccine in guinea pigs |
| topic | toxicology GLP Lassa vaccine reassortant virus |
| url | https://www.mdpi.com/2673-9879/5/2/26 |
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