Preclinical dose-ranging studies of a novel dry powder norovirus vaccine formulation

Abstract

Norovirus is the primary cause of viral gastroenteritis in humans with multiple genotypes currently circulating worldwide. The development of a successful norovirus vaccine is contingent on its ability to induce both systemic and mucosal antibody responses against a wide range of norovirus genotypes. Norovirus virus like particles (VLPs) are known to elicit systemic and mucosal immune responses when delivered intranasally. Incorporation of these VLPs into an intranasal powder vaccine offers the advantage of simplicity and induction of neutralizing systemic and mucosal antibodies. Nasal immunization, which provides the advantage of ease of administration and a mucosal delivery mechanism, faces the real issue of limited nasal residence time due to mucociliary clearance. Herein, we describe a novel dry powder (GelVac™) formulation of GI or GII.4 norovirus VLPs, two dominant circulating genotypes, to identify the optimal antigen dosages based on systemic and mucosal immune responses in guinea pigs. Systemic and mucosal immunogenicity of each of the VLPs was observed in a dose dependant manner. In addition, a boosting effect was observed after the second dosing of each VLP antigen. With the GelVac™ formulation, a total antigen dose of ≥15 µg was determined to be the maximally immunogenic dose for both GI and GII.4 norovirus VLP based on evaluation for 56 days. Taken together, these results indicate that norovirus VLPs could be used as potential vaccine candidates without using an immunostimilatory adjuvant and provides a basis for the development of a GelVac™ bivalent GI/GII.4 norovirus VLP vaccine.

Intranasal delivery of a bivalent norovirus vaccine formulated in an in situ gelling dry powder

“…The analytical characterization of the bivalent vaccine demonstrated that the bivalent powder was as described in previous work [14]. Norovirus GI and GII.4 VLP stocks were analyzed for the presence of intact VLPs by transmission electron microscopy prior to powder formulation.…”

Development of a synthetic Vi polysaccharide vaccine for typhoid fever

“…All reagents used for GelSite-OAc™ manufacturing were obtained from Sigma Chemical Co (St. Louis, MO). High-molecular-weight polygalacturonic acid (HPGA or GelSite ® ) was isolated from Aloe vera L [22, 23]. Its chemical and physical properties are summarized in Table 1.…”

Virus-Like Particles-Based Mucosal Nanovaccines

“…Pigs were i.n. immunized twice at 3-week intervals (Springer et al 2016). Test doses ranged 0.1-100 μg of VLPs.…”