Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine
We previously reported that topical imiquimod can improve the immunogenicity of the influenza vaccine. This study investigated another FDA-approved drug, miltefosine (MTF), as a vaccine adjuvant. Mice immunized with an influenza vaccine with or without MTF adjuvant were challenged by a lethal dose o...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/4/754 |
| _version_ | 1797544937289416704 |
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| author | Lu Lu Carol Ho-Yan Fong Anna Jinxia Zhang Wai-Lan Wu Iris Can Li Andrew Chak-Yiu Lee Thrimendra Kaushika Dissanayake Linlei Chen Ivan Fan-Ngai Hung Kwok-Hung Chan Hin Chu Kin-Hang Kok Kwok-Yung Yuen Kelvin Kai-Wang To |
| author_facet | Lu Lu Carol Ho-Yan Fong Anna Jinxia Zhang Wai-Lan Wu Iris Can Li Andrew Chak-Yiu Lee Thrimendra Kaushika Dissanayake Linlei Chen Ivan Fan-Ngai Hung Kwok-Hung Chan Hin Chu Kin-Hang Kok Kwok-Yung Yuen Kelvin Kai-Wang To |
| author_sort | Lu Lu |
| collection | DOAJ |
| description | We previously reported that topical imiquimod can improve the immunogenicity of the influenza vaccine. This study investigated another FDA-approved drug, miltefosine (MTF), as a vaccine adjuvant. Mice immunized with an influenza vaccine with or without MTF adjuvant were challenged by a lethal dose of influenza virus 3 or 7 days after vaccination. Survival, body weight, antibody response, histopathological changes, viral loads, cytokine levels, and T cell frequencies were compared. The MTF-adjuvanted vaccine (MTF-VAC) group had a significantly better survival rate than the vaccine-only (VAC) group, when administered 3 days (80% vs. 26.7%, <i>p</i> = 0.0063) or 7 days (96% vs. 65%, <i>p</i> = 0.0041) before influenza virus challenge. Lung damage was significantly ameliorated in the MTF-VAC group. Antibody response was significantly augmented in the MTF-VAC group against both homologous and heterologous influenza strains. There was a greater T follicular helper cell (T<sub>FH</sub>) response and an enhanced germinal center (GC) reaction in the MTF-VAC group. MTF-VAC also induced both T<sub>H</sub>1 and T<sub>H</sub>2 antigen-specific cytokine responses. MTF improved the efficacy of the influenza vaccine against homologous and heterologous viruses by improving the T<sub>FH</sub> and antibody responses. Miltefosine may also be used for other vaccines, including the upcoming vaccines for COVID-19. |
| first_indexed | 2024-03-10T14:07:32Z |
| format | Article |
| id | doaj.art-2445565afd0a45d8ad4e0a296a98452d |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T14:07:32Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-2445565afd0a45d8ad4e0a296a98452d2023-11-21T00:27:19ZengMDPI AGVaccines2076-393X2020-12-018475410.3390/vaccines8040754Repurposing of Miltefosine as an Adjuvant for Influenza VaccineLu Lu0Carol Ho-Yan Fong1Anna Jinxia Zhang2Wai-Lan Wu3Iris Can Li4Andrew Chak-Yiu Lee5Thrimendra Kaushika Dissanayake6Linlei Chen7Ivan Fan-Ngai Hung8Kwok-Hung Chan9Hin Chu10Kin-Hang Kok11Kwok-Yung Yuen12Kelvin Kai-Wang To13State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaState Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaWe previously reported that topical imiquimod can improve the immunogenicity of the influenza vaccine. This study investigated another FDA-approved drug, miltefosine (MTF), as a vaccine adjuvant. Mice immunized with an influenza vaccine with or without MTF adjuvant were challenged by a lethal dose of influenza virus 3 or 7 days after vaccination. Survival, body weight, antibody response, histopathological changes, viral loads, cytokine levels, and T cell frequencies were compared. The MTF-adjuvanted vaccine (MTF-VAC) group had a significantly better survival rate than the vaccine-only (VAC) group, when administered 3 days (80% vs. 26.7%, <i>p</i> = 0.0063) or 7 days (96% vs. 65%, <i>p</i> = 0.0041) before influenza virus challenge. Lung damage was significantly ameliorated in the MTF-VAC group. Antibody response was significantly augmented in the MTF-VAC group against both homologous and heterologous influenza strains. There was a greater T follicular helper cell (T<sub>FH</sub>) response and an enhanced germinal center (GC) reaction in the MTF-VAC group. MTF-VAC also induced both T<sub>H</sub>1 and T<sub>H</sub>2 antigen-specific cytokine responses. MTF improved the efficacy of the influenza vaccine against homologous and heterologous viruses by improving the T<sub>FH</sub> and antibody responses. Miltefosine may also be used for other vaccines, including the upcoming vaccines for COVID-19.https://www.mdpi.com/2076-393X/8/4/754influenza vaccinevaccineadjuvantT<sub>FH</sub>miltefosine |
| spellingShingle | Lu Lu Carol Ho-Yan Fong Anna Jinxia Zhang Wai-Lan Wu Iris Can Li Andrew Chak-Yiu Lee Thrimendra Kaushika Dissanayake Linlei Chen Ivan Fan-Ngai Hung Kwok-Hung Chan Hin Chu Kin-Hang Kok Kwok-Yung Yuen Kelvin Kai-Wang To Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine Vaccines influenza vaccine vaccine adjuvant T<sub>FH</sub> miltefosine |
| title | Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine |
| title_full | Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine |
| title_fullStr | Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine |
| title_full_unstemmed | Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine |
| title_short | Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine |
| title_sort | repurposing of miltefosine as an adjuvant for influenza vaccine |
| topic | influenza vaccine vaccine adjuvant T<sub>FH</sub> miltefosine |
| url | https://www.mdpi.com/2076-393X/8/4/754 |
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