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 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.