Single Dose of Attenuated Vaccinia Viruses Expressing H5 Hemagglutinin Affords Rapid and Long-Term Protection Against Lethal Infection with Highly Pathogenic Avian Influenza A H5N1 Virus in Mice and Monkeys
Background/Objectives: In preparation for a potential pandemic caused by the H5N1 highly pathogenic avian influenza (HPAI) virus, pre-pandemic vaccines against several viral clades have been developed and stocked worldwide. Although these vaccines are well tolerated, their immunogenicity and cross-r...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/13/1/74 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832587393395326976 |
|---|---|
| author | Fumihiko Yasui Keisuke Munekata Tomoko Fujiyuki Takeshi Kuraishi Kenzaburo Yamaji Tomoko Honda Sumiko Gomi Misako Yoneda Takahiro Sanada Koji Ishii Yoshihiro Sakoda Hiroshi Kida Shosaku Hattori Chieko Kai Michinori Kohara |
| author_facet | Fumihiko Yasui Keisuke Munekata Tomoko Fujiyuki Takeshi Kuraishi Kenzaburo Yamaji Tomoko Honda Sumiko Gomi Misako Yoneda Takahiro Sanada Koji Ishii Yoshihiro Sakoda Hiroshi Kida Shosaku Hattori Chieko Kai Michinori Kohara |
| author_sort | Fumihiko Yasui |
| collection | DOAJ |
| description | Background/Objectives: In preparation for a potential pandemic caused by the H5N1 highly pathogenic avian influenza (HPAI) virus, pre-pandemic vaccines against several viral clades have been developed and stocked worldwide. Although these vaccines are well tolerated, their immunogenicity and cross-reactivity with viruses of different clades can be improved. Methods: To address this aspect, we generated recombinant influenza vaccines against H5-subtype viruses using two different strains of highly attenuated vaccinia virus (VACV) vectors. Results: rLC16m8-mcl2.2 hemagglutinin (HA) and rLC16m8-mcl2.3.4 HA consisted of a recombinant LC16m8 vector encoding the HA protein from clade 2.2 or clade 2.3.4 viruses (respectively); rDIs-mcl2.2 HA consisted of a recombinant DIs vector encoding the HA protein from clade 2.2. A single dose of rLC16m8-mcl2.2 HA showed rapid (1 week after vaccination) and long-term protection (20 months post-vaccination) in mice against the HPAI H5N1 virus. Moreover, cynomolgus macaques immunized with rLC16m8-mcl2.2 HA exhibited long-term protection when challenged with a heterologous clade of the HPAI H5N1 virus. Although the DIs strain is unable to grow in most mammalian cells, rDIs-mcl2.2 HA also showed rapid and long-lasting effects against HPAI H5N1 virus infection. Notably, the protective efficacy of rDIs-mcl2.2 HA was comparable to that of rLC16m8-mcl2.2 HA. Furthermore, these vaccines protected animals previously immunized with VACVs from a lethal challenge with the HPAI H5N1 virus. Conclusions: These results suggest that both rLC16m8-mcl2.2 HA and rDIs-mcl2.2 HA are effective in preventing HPAI H5N1 virus infection, and rDIs-mcl2.2 HA is a promising vaccine candidate against H5 HA-subtype viruses. |
| format | Article |
| id | doaj-art-da30379b330342528d780b01f1fdd731 |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-da30379b330342528d780b01f1fdd7312025-01-24T13:51:51ZengMDPI AGVaccines2076-393X2025-01-011317410.3390/vaccines13010074Single Dose of Attenuated Vaccinia Viruses Expressing H5 Hemagglutinin Affords Rapid and Long-Term Protection Against Lethal Infection with Highly Pathogenic Avian Influenza A H5N1 Virus in Mice and MonkeysFumihiko Yasui0Keisuke Munekata1Tomoko Fujiyuki2Takeshi Kuraishi3Kenzaburo Yamaji4Tomoko Honda5Sumiko Gomi6Misako Yoneda7Takahiro Sanada8Koji Ishii9Yoshihiro Sakoda10Hiroshi Kida11Shosaku Hattori12Chieko Kai13Michinori Kohara14Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, JapanDepartment of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, JapanInfectious Disease Control Science, Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8505, JapanAnimal Laboratory of Injurious Animals, The Institute of Medical Science, The University of Tokyo, 802, Tean Sude, Setouchi-cho, Oshima-gun, Kagoshima 894-1531, JapanDepartment of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, JapanDepartment of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, JapanDepartment of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, JapanInfectious Disease Control Science, Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8505, JapanDepartment of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, JapanCenter for Quality Management Systems, National Institute of Infectious Diseases, 4-7-1, Gakuen, Musashi-murayama, Tokyo 208-0011, JapanLaboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo 060-0818, JapanInstitute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo 001-0021, JapanAnimal Laboratory of Injurious Animals, The Institute of Medical Science, The University of Tokyo, 802, Tean Sude, Setouchi-cho, Oshima-gun, Kagoshima 894-1531, JapanInfectious Disease Control Science, Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8505, JapanDepartment of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, JapanBackground/Objectives: In preparation for a potential pandemic caused by the H5N1 highly pathogenic avian influenza (HPAI) virus, pre-pandemic vaccines against several viral clades have been developed and stocked worldwide. Although these vaccines are well tolerated, their immunogenicity and cross-reactivity with viruses of different clades can be improved. Methods: To address this aspect, we generated recombinant influenza vaccines against H5-subtype viruses using two different strains of highly attenuated vaccinia virus (VACV) vectors. Results: rLC16m8-mcl2.2 hemagglutinin (HA) and rLC16m8-mcl2.3.4 HA consisted of a recombinant LC16m8 vector encoding the HA protein from clade 2.2 or clade 2.3.4 viruses (respectively); rDIs-mcl2.2 HA consisted of a recombinant DIs vector encoding the HA protein from clade 2.2. A single dose of rLC16m8-mcl2.2 HA showed rapid (1 week after vaccination) and long-term protection (20 months post-vaccination) in mice against the HPAI H5N1 virus. Moreover, cynomolgus macaques immunized with rLC16m8-mcl2.2 HA exhibited long-term protection when challenged with a heterologous clade of the HPAI H5N1 virus. Although the DIs strain is unable to grow in most mammalian cells, rDIs-mcl2.2 HA also showed rapid and long-lasting effects against HPAI H5N1 virus infection. Notably, the protective efficacy of rDIs-mcl2.2 HA was comparable to that of rLC16m8-mcl2.2 HA. Furthermore, these vaccines protected animals previously immunized with VACVs from a lethal challenge with the HPAI H5N1 virus. Conclusions: These results suggest that both rLC16m8-mcl2.2 HA and rDIs-mcl2.2 HA are effective in preventing HPAI H5N1 virus infection, and rDIs-mcl2.2 HA is a promising vaccine candidate against H5 HA-subtype viruses.https://www.mdpi.com/2076-393X/13/1/74vaccinia virus vectorcross-clade protectionhemagglutinin proteinrapid protectionlong-term protection |
| spellingShingle | Fumihiko Yasui Keisuke Munekata Tomoko Fujiyuki Takeshi Kuraishi Kenzaburo Yamaji Tomoko Honda Sumiko Gomi Misako Yoneda Takahiro Sanada Koji Ishii Yoshihiro Sakoda Hiroshi Kida Shosaku Hattori Chieko Kai Michinori Kohara Single Dose of Attenuated Vaccinia Viruses Expressing H5 Hemagglutinin Affords Rapid and Long-Term Protection Against Lethal Infection with Highly Pathogenic Avian Influenza A H5N1 Virus in Mice and Monkeys Vaccines vaccinia virus vector cross-clade protection hemagglutinin protein rapid protection long-term protection |
| title | Single Dose of Attenuated Vaccinia Viruses Expressing H5 Hemagglutinin Affords Rapid and Long-Term Protection Against Lethal Infection with Highly Pathogenic Avian Influenza A H5N1 Virus in Mice and Monkeys |
| title_full | Single Dose of Attenuated Vaccinia Viruses Expressing H5 Hemagglutinin Affords Rapid and Long-Term Protection Against Lethal Infection with Highly Pathogenic Avian Influenza A H5N1 Virus in Mice and Monkeys |
| title_fullStr | Single Dose of Attenuated Vaccinia Viruses Expressing H5 Hemagglutinin Affords Rapid and Long-Term Protection Against Lethal Infection with Highly Pathogenic Avian Influenza A H5N1 Virus in Mice and Monkeys |
| title_full_unstemmed | Single Dose of Attenuated Vaccinia Viruses Expressing H5 Hemagglutinin Affords Rapid and Long-Term Protection Against Lethal Infection with Highly Pathogenic Avian Influenza A H5N1 Virus in Mice and Monkeys |
| title_short | Single Dose of Attenuated Vaccinia Viruses Expressing H5 Hemagglutinin Affords Rapid and Long-Term Protection Against Lethal Infection with Highly Pathogenic Avian Influenza A H5N1 Virus in Mice and Monkeys |
| title_sort | single dose of attenuated vaccinia viruses expressing h5 hemagglutinin affords rapid and long term protection against lethal infection with highly pathogenic avian influenza a h5n1 virus in mice and monkeys |
| topic | vaccinia virus vector cross-clade protection hemagglutinin protein rapid protection long-term protection |
| url | https://www.mdpi.com/2076-393X/13/1/74 |
| work_keys_str_mv | AT fumihikoyasui singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT keisukemunekata singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT tomokofujiyuki singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT takeshikuraishi singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT kenzaburoyamaji singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT tomokohonda singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT sumikogomi singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT misakoyoneda singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT takahirosanada singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT kojiishii singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT yoshihirosakoda singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT hiroshikida singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT shosakuhattori singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT chiekokai singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys AT michinorikohara singledoseofattenuatedvacciniavirusesexpressingh5hemagglutininaffordsrapidandlongtermprotectionagainstlethalinfectionwithhighlypathogenicavianinfluenzaah5n1virusinmiceandmonkeys |