Injectable Excipients as Novel Influenza Vaccine Adjuvants

Abstract

Influenza outbreaks can be either seasonal or pandemic. Vaccination is an effective strategy to control influenza; however, the efficacy of the currently available inactivated influenza virus vaccines is suboptimal, especially in the elderly. Vaccine efficacy can be improved by the addition of adjuvants, but few adjuvants have been approved for human vaccines. To explore novel, safe, and effective adjuvants for influenza vaccines, here we used a mouse model to screen 46 injectable drug additives approved in Japan. Of these 46 candidates, we identified 20 compounds that enhanced the efficacy of the split influenza HA vaccine against lethal virus challenge. These 20 compounds included 15 novel adjuvant candidates and 5 compounds with previously reported adjuvant effects for other antigens but not for influenza vaccine. Given that these additives are already approved for human use, the hurdle for their clinical use as novel and effective adjuvants for influenza or other vaccines is lower than for other adjuvant candidates whose safety profiles are unknown.

Identification of Novel Adjuvants for Ebola Virus-Like Particle Vaccine

“…These compounds have all been approved for intramuscular or subcutaneous administration in humans in Japan, including 14 compounds approved by the FDA ( Table S1 ). Of the 24 compounds, 21 were found to have adjuvant effects on seasonal influenza vaccine in our previous study [ 31 ].…”

“…Ideal adjuvants would be safe in humans and effectively enhance vaccine efficacy. Previously, we demonstrated that several injectable excipients, which are approved for human use in Japan, enhanced the efficacy of influenza vaccine against lethal virus challenge in a mouse model [ 31 ]. In the present study, we screened 24 injectable excipients, including 14 FDA-approved compounds ( Table S1 ), and identified six novel adjuvant candidates that significantly enhanced the humoral response to Ebola VLP vaccine in mice ( Figure 2 ), although the neutralizing antibody titers were not determined in this study.…”

“…Virus-specific antibody titers in the mouse sera were determined by using a modified ELISA as previously described [ 31 , 40 , 41 , 42 ]. Briefly, 96-well ELISA plates (IWAKI) were coated with 5 µg/mL of purified GP mutant protein solution, which was produced as described in the Supplementary Information , overnight at 4 °C (50 µL/well).…”

“…The major advantage of this system is that it can yield high-levels of VLPs and be easily scaled-up for manufacturing [ 24 , 26 ]; however, protein-based vaccines may not be as immunogenic as live vaccines [ 29 , 30 ] and, therefore, the addition of appropriate adjuvants may improve their efficacy and enhance immune responses. Previously, we showed the usability of certain injectable excipients, approved for human use and with good safety profiles, to enhance the humoral immune responses to a seasonal influenza vaccine [ 31 ]. To explore adjuvant candidates that are safe and enhance the immunogenicity of Ebola VLP vaccine, here we screened 24 injectable excipients for adjuvant effects with an Ebola VLP vaccine in mice.…”

Food Additives as Novel Influenza Vaccine Adjuvants

“…Virus-specific antibody titers in sera were determined using a modified ELISA as previously described [23,24]. Briefly, 96-well ELISA plates (IWAKI) were coated with 6 µg/mL of inactivated and purified CA07 virus solution overnight at 4 • C (50 µL/well).…”