Membrane-bound IL-12 and IL-23 serve as potent mucosal adjuvants when co-presented on whole inactivated influenza vaccines

Abstract

BackgroundPotent and safe adjuvants are needed to improve the efficacy of parenteral and mucosal vaccines. Cytokines, chemokines and growth factors have all proven to be effective immunomodulatory adjuvants when administered with a variety of antigens. We have previously evaluated the efficacy of membrane-anchored interleukins (IL) such as IL-2 and IL-4 co-presented as Cytokine-bearing Influenza Vaccines (CYT-IVACs) using a mouse model of influenza challenge.FindingsHere, we describe studies evaluating the parenteral and mucosal adjuvanticity of membrane-bound IL-12 and IL-23 CYT-IVACs in young adult mice. Mucosal immunization using IL-12 and IL-23 bearing whole influenza virus vaccine (WIV) was more effective at eliciting virus-specific nasal IgA and reducing viral lung burden following challenge compared to control WIV vaccinated animals. Both IL-12 and IL-23 bearing WIV elicited the highest anti-viral IgA levels in serum and nasal washes.ConclusionsThis study highlights for the first time the mucosal adjuvant potential of IL-12 and IL-23 CYT-IVAC formulations in eliciting mucosal immune responses and reducing viral lung burden. The co-presentation of immunomodulators in direct context with viral antigen in whole inactivated viral vaccines may provide a means to significantly lower the dose of vaccine required for protection.

Interleukin 12-containing influenza virus-like-particle vaccine elevate its protective activity against heterotypic influenza virus infection

“…The IL-12–40/35 genes were also synthesised by GENEWIZ. Briefly, IL-12–40/35 was constructed by combining two IL-12 subunits (p40 and p35) with a glycine linker (L1) such that p40 was located at the N-terminus, and the membrane anchor region, which consists of the influenza strain WSN (H1N1) HA membrane-anchoring domain ( Figure 1 D), was located in the C-terminus [ 25 ]. Then, the IL-12–40/35 gene was inserted downstream of the pFastBac1 polyhedrin promotor.…”

“…First, we attempted to effectively and rapidly produce inexpensive bivalent and multivalent vaccines in silkworms on a large scale to provide high-quality vaccines for the poultry and healthcare industries. Then, we inserted membrane-anchored interleukin (IL)-12 into VLP vaccines to enhance mucosal immune responses and elicit cellular immune responses [ 25 , 26 , 27 , 28 ]. Khan et al.…”

“…Khan et al. [ 25 ] demonstrated that coexpression of membrane-anchored IL-12 and IL-23 with influenza vaccines resulted in enhanced mucosal immune responses. Here, we describe an effective multiple-infection system that can be used to synthesise bivalent or VLP vaccines containing IL-12 and multiple HA VLP antigens.…”

Alkyl polyglycoside, a highly promising adjuvant in intranasal split influenza vaccines

“…As such, various approaches have been investigated to improve immunogenicity of i.n. influenza vaccines in recent years, including the use of adjuvants such as CTA1-DD (Cholera toxin subunit A), 12 IL-12, IL-23 13 , poly I:C (TLR3 agonist), [14][15][16] and CS, 17 as well as genetically modified whole viruses. 18 Several delivery systems have been developed to address this issue, including liposomes, [19][20][21][22] nanoparticles, 23 and microspheres 24 ; however, all of these attempts are still at pre-clinical stage maybe due to unsatisfactory immunogenicity, safety concern or complexity in production process.…”

Current and next generation influenza vaccines: Formulation and production strategies

“…Additionally, these novel 126 antigens often need to be formulated with excipients and adju-127 vants to be sufficiently immunogenic. While important, the devel-128 opment of alternative administration methods and devices for 129 influenza vaccines is not within the scope of this current review, 130 and has been thoroughly reviewed by Amorij et al previously 131 [7]. In this review, we will discuss advances in immunological, for-132 mulation and production aspects for current and promising novel 133 influenza vaccine antigens, and discuss their potential to solve 134 the limitations of influenza vaccines today.…”