Improved Immune Response to Recombinant Influenza Nucleoprotein Formulated with ISCOMATRIX

Abstract

Current influenza vaccines elicit antibodies effective against homologous strains, but new strategies are urgently needed for protection against emerging epidemic or pandemic strains. Although influenza vaccine candidates based on the viral nucleoprotein (NP) or matrix protein do not elicit sterilizing immunity, they have the advantage of inducing immunity that may cover a larger number of viral strains. In this study, recombinant NP produced in Escherichia coli was purified and formulated in combination with the adjuvant ISCOMATRIX. This formulation increased a NP-specific immunity in mice, with a Th1 profile, and may constitute a promising low-cost influenza vaccine candidate, with ability to stimulate humoral and cellular immune responses.

Intranasal Delivery of Influenza rNP Adjuvanted with c-di-AMP Induces Strong Humoral and Cellular Immune Responses and Provides Protection against Virus Challenge

“…NP was chosen as antigen due to the fact that this protein is one of the most promising candidates for the development of an influenza vaccine with broader cross-protective activity. In addition, rNP could be produced in E. coli at high yields and comparatively low costs [42]. To this end, groups of BALB/c mice were immunized by intranasal route with two doses of 10 µg of rNP alone, or co-administered with 10 µg of c-di-AMP, at an interval of three weeks.…”

“…The recombinant influenza nucleoprotein (rNP), derived from the influenza strain A/PR/8/34 (H1N1), was synthesized and purified as previously described [42]. The synthesis and purification of the mucosal adjuvant c-di-AMP was described in Ebensen et al [41].…”

Development of adjuvant nanocarrier systems for seasonal influenza A (H3N2) vaccine based on Astragaloside VII and gum tragacanth (APS)

“…ISCOMATRIX and ISCOMs (40-50 nm). ISCOMATRIX adjuvanted recombinant influenza nucleoprotein demonstrated high anti-IgG antibody and strong Th1 immune response [33][34][35].…”

Development of a universal CTL-based vaccine for influenza

“…In our experience, analysis of the values of IgG subtypes and interleukins in the sera of mice that had been immunized with IMX-formulated rNP clearly indicated that the response obtained had a strong Th1 profile. 63 These experiments also showed the generation of high titers of IgG anti-NP. This should be also taken into account, since it has been demonstrated that specific high titers obtained after immunization of mice with rNP contributed to a rapid antibody-dependent elimination of the year 2009 H1N1 pandemic virus strain and that high anti NP titers correlated with an increase in the CD8 + response.…”