Dataset Information

Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine.

ABSTRACT: 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%, p = 0.0063) or 7 days (96% vs. 65%, p = 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_FH) response and an enhanced germinal center (GC) reaction in the MTF-VAC group. MTF-VAC also induced both T_H1 and T_H2 antigen-specific cytokine responses. MTF improved the efficacy of the influenza vaccine against homologous and heterologous viruses by improving the T_FH and antibody responses. Miltefosine may also be used for other vaccines, including the upcoming vaccines for COVID-19.

SUBMITTER: Lu L

PROVIDER: S-EPMC7768360 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine.

Lu Lu L Fong Carol Ho-Yan CH Zhang Anna Jinxia AJ Wu Wai-Lan WL Li Iris Can IC Lee Andrew Chak-Yiu AC Dissanayake Thrimendra Kaushika TK Chen Linlei L Hung Ivan Fan-Ngai IF Chan Kwok-Hung KH Chu Hin H Kok Kin-Hang KH Yuen Kwok-Yung KY To Kelvin Kai-Wang KK

Vaccines 20201211 4

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-adjuva ...[more]

PMID: 33322574

Similar Datasets

Project description:Squalene-based oil-in-water (O/W) emulsions have been used as effective and safe adjuvants in approved influenza vaccines. However, there are concerns regarding the safety and side effects of increasing risk of narcolepsy. In present study, novel O/W microemulsions (MEs) containing wheat germ oil, D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) and Cremophor EL (CreEL) or Solutol HS15 were formulated with/without a cationic surfactant, cetyltrimethylammonium bromide (CTAB) and then sterilized by autoclaving. Their physical properties and biological efficacies were evaluated. The results demonstrated that autoclaving reduced the droplet size to ∼20 nm with narrow size distributions resulting in monodisperse systems with good stability up to 3 years. Hemolytic activity, viscosity, pH, and osmolality were appropriate for parenteral use. Bovine serum albumin (BSA), a model antigen, after mixing with MEs retained the protein integrity, assessed by SDS-PAGE and CD spectroscopy. Greater percentages of 28SC cell viability were observed from CreEL-based MEs. Uptake of FITC-BSA-MEs increased with the increasing concentration of CTAB confirmed by CLSM images. Furthermore, cationic CreEL-based MEs could induce Th1 cytokine synthesis with an increase in TNF-α and IL-12 levels and a decrease in IL-10 level. In vivo immunization study in mice of adjuvants admixed with influenza virus solution revealed that nonionic and selected cationic CreEL-MEs enhanced immune responses as measured by influenza-specific serum antibody titers and hemagglutination inhibition titers. Particularly, cationic CreEL-based ME showed better humoral and cellular immunity with higher IgG2a titer than nonionic CreEL-based ME and antigen alone. No differences in immune responses were observed between mice immunized with selected cationic CreEL-based ME and marketed adjuvant. In addition, the selected ME induced antigen-sparing while retained immune stimulating effects compared to antigen alone. No inflammatory change in muscle fiber structure was observed. Accordingly, the developed cationic CreEL-based ME had potential as novel adjuvant for parenteral influenza vaccine.

Dataset Information

Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine.

Publications

Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets