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 (TFH) response and an enhanced germinal center (GC) reaction in the MTF-VAC group. MTF-VAC also induced both TH1 and TH2 antigen-specific cytokine responses. MTF improved the efficacy of the influenza vaccine against homologous and heterologous viruses by improving the TFH and antibody responses. Miltefosine may also be used for other vaccines, including the upcoming vaccines for COVID-19.
Highlights
Pandemic, seasonal, and avian influenza viruses are associated with significant morbidity and mortality [1,2]
We have previously shown that intraperitoneal imiquimod, a toll-like receptor 7 (TLR7) agonist, can improve vaccine efficacy for both A(H1N1) and the avian influenza virus A(H7N9) in a mouse model [12,13]
To determine the adjuvant effect of MTF, mice were immunized with an influenza vaccine with or without MTF, and were challenged by 415742Md 7 days after vaccination (Figure 1A)
Summary
Seasonal, and avian influenza viruses are associated with significant morbidity and mortality [1,2]. Available antivirals have limited efficacy in the treatment of influenza virus infection, especially for severe cases [3]. Vaccines have played a pivotal role in the prevention of influenza and have been shown to reduce complications [4]. The influenza vaccine alone, or with the pneumococcal vaccine, has been shown to reduce the incidence of myocardial infarction and stroke [5]. The currently available influenza vaccine only has an estimated overall efficacy of about 60% [4]. A meta-analysis showed that the pooled vaccine efficacy against influenza virus A(H3N2) is only
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