Advax augments B and T cell responses upon influenza vaccination via the respiratory tract and enables complete protection of mice against lethal influenza virus challenge

Abstract

Administration of influenza vaccines via the respiratory tract has potential benefits over conventional parenteral administration, inducing immunity directly at the site of influenza exposure as well as being needle free. In this study, we investigated the suitability of Advax™, a stable particulate polymorph of inulin, also referred to as delta inulin, as a mucosal adjuvant for whole inactivated influenza vaccine (WIV) administered either as a liquid or dry powder formulation. Spray freeze-drying produced Advax-adjuvanted WIV powder particles in a size range (1-5 μm) suitable for inhalation. The physical and biological characteristics of both WIV and Advax remained unaltered both by admixing WIV with Advax and by spray freeze drying. Upon intranasal or pulmonary immunization, both liquid and dry powder formulations containing Advax induced significantly higher systemic, mucosal and cellular immune responses than non-adjuvanted WIV formulations. Furthermore, pulmonary immunization with Advax-adjuvanted WIV led to robust memory B cell responses along with an increase of lung localization factors i.e. CXCR3, CD69, and CD103. A less pronounced but still positive effect of Advax was seen on memory T cell responses. In contrast to animals immunized with WIV alone, all animals pulmonary immunized with a single dose of Advax-adjuvanted WIV were fully protected with no visible clinical symptoms against a lethal dose of influenza virus. These data confirm that Advax is a potent mucosal adjuvant that boosts vaccine-induced humoral and cellular immune responses both in the lung and systemically with major positive effects on B-cell memory and complete protection against live virus. Hence, respiratory tract immunization, particularly via the lungs, with Advax-adjuvanted WIV formulation as a liquid or dry powder is a promising alternative to parenteral influenza vaccination.

Mucosal delivery of a multistage subunit vaccine promotes development of lung-resident memory T cells and affords interleukin-17-dependant protection against pulmonary tuberculosis

“…Advax is a particulate polysaccharide adjuvant with a low inflammatory profile that has proven to be safe and a strong inducer of vaccine immunogenicity in humans, thus making it an ideal candidate for mucosal administration [18] [19]. Notably, it was recently shown to provide safe and effective enhancement of influenza vaccine immunity when administered via the intrapulmonary route in different animal models [20,21].…”

“…https://doi.org/10.1101/2020.02.25.964312 doi: bioRxiv preprint 15 effect of the vaccine was associated with targeted expansion of lung-resident T RM and was dependent on IL-17 recruitment of phagocytic cells to the lung and enhanced priming of T cells in the mLN. As Advax-containing vaccines have proven safe and immunogenic in human trials against viral infection and allergy [19,45,46] and are safe and effective in pre-clinical trials as inhaled formulations [21], CysVac2/Advax is a promising candidate for assessment of safety, immunogenicity and efficacy as a pulmonary vaccine in human subjects.…”

Passive inhalation of dry powder influenza vaccine formulations completely protects chickens against H5N1 lethal viral challenge

“…Also, the biological activity of BLP was found to be well preserved during SFD. Previous studies have shown that administration of BLP or Advax adjuvanted influenza vaccine formulations via the respiratory tract results in substantial augmentation of systemic and mucosal immune responses in mice [16,[43][44][45][46]. In this study we showed that after active administration, systemic immune responses (serum IgY titers) after one immunization were predominantly enhanced by Advax whereas after two immunizations they (serum IgY, HI titers, micro-neutralization titers) were mainly enhanced by BLP.…”

Development of an Orodispersible Film Containing Stabilized Influenza Vaccine

“…The virus was produced in the allantoic cavity of 11-day-old embryonated hens' eggs. The virus was purified and inactivated as described by Tomar et al to obtain WIV [21,22]. WIV was derived from the same strain as previously published [21,22].…”

“…The virus was purified and inactivated as described by Tomar et al to obtain WIV [21,22]. WIV was derived from the same strain as previously published [21,22]. The size of WIV (around 185 nm) together with other physico-chemical properties of WIV were described in these papers.…”