Intranasal M2SR and BM2SR Vaccine Viruses Do Not Shed or Transmit in Ferrets
Background/Objectives: Live influenza vaccines are considered to stimulate better overall immune responses but are associated with safety concerns regarding shedding and the potential for transmission or reassortment with wild-type influenza viruses. Intranasal M2SR and BM2SR (M2- and BM2-deficient...
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MDPI AG
2024-10-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/12/11/1228 |
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| author | Yasuko Hatta Lindsay Hill-Batorski Michael J. Moser David Marshall David A. Boltz Landon Westfall Renee Herber Sally Sarawar Pamuk Bilsel |
| author_facet | Yasuko Hatta Lindsay Hill-Batorski Michael J. Moser David Marshall David A. Boltz Landon Westfall Renee Herber Sally Sarawar Pamuk Bilsel |
| author_sort | Yasuko Hatta |
| collection | DOAJ |
| description | Background/Objectives: Live influenza vaccines are considered to stimulate better overall immune responses but are associated with safety concerns regarding shedding and the potential for transmission or reassortment with wild-type influenza viruses. Intranasal M2SR and BM2SR (M2- and BM2-deficient single replication), intranasal influenza viruses, have shown promise as broadly cross-reactive next-generation influenza vaccines. The replication deficiency, shedding, and transmissibility of M2SR/BM2SR viruses were evaluated in a ferret model. Methods: Wild-type influenza A and B control viruses replicated in upper respiratory organs and transmitted to both direct and aerosol contact ferrets, whereas M2SR and BM2SR influenza vaccine viruses were not detected in any tissues or in nasal washes after inoculation and were not recovered from any direct or aerosol contact ferrets. Mice were simultaneously infected with wild-type influenza A and M2SR viruses to assess reassortment potential. Sequence and PCR analyses of the genome recovered from individual virus plaques isolated from lung homogenates identified the origin of the segments as exclusively from the replicating wild-type virus. Results: These results indicate that M2SR and BM2SR influenza vaccine viruses are attenuated, do not shed or transmit, and have a low probability for reassortment after coinfection. Absence of shedding was further demonstrated in nasal swabs taken from subjects who were inoculated with H3N2 M2SR in a previously described Phase 1 clinical study. Conclusions: These results indicate that M2SR/BM2SR viruses have the potential to be used in a broader population range than current live influenza vaccines. |
| format | Article |
| id | doaj-art-63c2e4287c214b30aa4eff9101548ee2 |
| institution | OA Journals |
| issn | 2076-393X |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-63c2e4287c214b30aa4eff9101548ee22025-08-20T01:54:08ZengMDPI AGVaccines2076-393X2024-10-011211122810.3390/vaccines12111228Intranasal M2SR and BM2SR Vaccine Viruses Do Not Shed or Transmit in FerretsYasuko Hatta0Lindsay Hill-Batorski1Michael J. Moser2David Marshall3David A. Boltz4Landon Westfall5Renee Herber6Sally Sarawar7Pamuk Bilsel8FluGen, Inc., Madison, WI 53711, USAFluGen, Inc., Madison, WI 53711, USAFluGen, Inc., Madison, WI 53711, USAFluGen, Inc., Madison, WI 53711, USAIIT Research Institute, Chicago, IL 60616, USAIIT Research Institute, Chicago, IL 60616, USAFluGen, Inc., Madison, WI 53711, USAThe BioMedical Research Institute of Southern California, Oceanside, CA 92056, USAFluGen, Inc., Madison, WI 53711, USABackground/Objectives: Live influenza vaccines are considered to stimulate better overall immune responses but are associated with safety concerns regarding shedding and the potential for transmission or reassortment with wild-type influenza viruses. Intranasal M2SR and BM2SR (M2- and BM2-deficient single replication), intranasal influenza viruses, have shown promise as broadly cross-reactive next-generation influenza vaccines. The replication deficiency, shedding, and transmissibility of M2SR/BM2SR viruses were evaluated in a ferret model. Methods: Wild-type influenza A and B control viruses replicated in upper respiratory organs and transmitted to both direct and aerosol contact ferrets, whereas M2SR and BM2SR influenza vaccine viruses were not detected in any tissues or in nasal washes after inoculation and were not recovered from any direct or aerosol contact ferrets. Mice were simultaneously infected with wild-type influenza A and M2SR viruses to assess reassortment potential. Sequence and PCR analyses of the genome recovered from individual virus plaques isolated from lung homogenates identified the origin of the segments as exclusively from the replicating wild-type virus. Results: These results indicate that M2SR and BM2SR influenza vaccine viruses are attenuated, do not shed or transmit, and have a low probability for reassortment after coinfection. Absence of shedding was further demonstrated in nasal swabs taken from subjects who were inoculated with H3N2 M2SR in a previously described Phase 1 clinical study. Conclusions: These results indicate that M2SR/BM2SR viruses have the potential to be used in a broader population range than current live influenza vaccines.https://www.mdpi.com/2076-393X/12/11/1228M2-deficientsheddingliveinfluenzaM2BM2 |
| spellingShingle | Yasuko Hatta Lindsay Hill-Batorski Michael J. Moser David Marshall David A. Boltz Landon Westfall Renee Herber Sally Sarawar Pamuk Bilsel Intranasal M2SR and BM2SR Vaccine Viruses Do Not Shed or Transmit in Ferrets Vaccines M2-deficient shedding live influenza M2 BM2 |
| title | Intranasal M2SR and BM2SR Vaccine Viruses Do Not Shed or Transmit in Ferrets |
| title_full | Intranasal M2SR and BM2SR Vaccine Viruses Do Not Shed or Transmit in Ferrets |
| title_fullStr | Intranasal M2SR and BM2SR Vaccine Viruses Do Not Shed or Transmit in Ferrets |
| title_full_unstemmed | Intranasal M2SR and BM2SR Vaccine Viruses Do Not Shed or Transmit in Ferrets |
| title_short | Intranasal M2SR and BM2SR Vaccine Viruses Do Not Shed or Transmit in Ferrets |
| title_sort | intranasal m2sr and bm2sr vaccine viruses do not shed or transmit in ferrets |
| topic | M2-deficient shedding live influenza M2 BM2 |
| url | https://www.mdpi.com/2076-393X/12/11/1228 |
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