Abstract
Trivalent inactivated vaccines (TIV) against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6′-dibehenate, CAF01) was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines.
Highlights
Efforts to prevent or minimize the impact of seasonal influenza in the second part of the 20th century have focused on the use of vaccines [1]
This study demonstrates that the novel liposomal adjuvant cationic adjuvant formulation 01 (CAF01) potentiates the humoral response and adds an additional cellmediated immune (CMI) response to the response promoted by a commercially available split vaccine
In spite of the limitations of a response based on only humoral immunity, antibodies are still the main response induced by influenza vaccines [9]
Summary
Efforts to prevent or minimize the impact of seasonal influenza in the second part of the 20th century have focused on the use of vaccines [1]. The quality of the immune response conferred by the available killed virus vaccines has been debated and is almost solely focused on a humoral response directed against highly variable surface proteins [9], whereas the induction of cellmediated immune (CMI) responses is negligible [10,11]. It has been shown during natural infections that T-cells target primarily conserved proteins from the inner part of the virion that may mediate cross-protection against heterologous strains [12] and long-lived protection [13]. The ideal vaccine to fight both epidemic and pandemic influenza should induce both a humoral and a cellular immune response with only one injection of a minimal dose [14]
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