Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials

Vijayan, Veena; Mohapatra, Adityanarayan; Uthaman, Saji; Park, In-Kyu

Moon et al. reported the development of a recombinant antigen derived from the circumsporozoite protein, which is the most predominant membrane protein on sporozoites. Their initial work stated that this recombinant antigen, when mixed with conventional antigens could elicit an antigen-specific antibody response [21] . They used a lipid enveloped polymeric NP, and conjugated the malarial antigen into the lipid membrane with an immunostimulatory molecule monophosphoryl lipid A incorporated into the lipid membranes, which resulted in a pathogen-mimicking NP vaccine [21] . Another study suggested that antigen-loaded NPs that display monophosphoryl lipid A (MPLA) and further encapsulation with adjuvant CpG motifs and model antigen Ovalbumin could act as an efficient bacterial vaccine [93] . In that study, CpG potency was found to be enhanced when it was encapsulated inside the NP, which in turn highlights the importance of the biomimetic presentation of pathogen-associated molecular patterns. Because of MPLA with CpG, the pro-inflammatory, antigen-specific T helper 1 (Th 1) cellular and antibody-mediated immune responses were significantly increased [93] . Sahu et al. [23] reported the use of monophosphoryl lipid A (MPLA) NPs loaded with a Hepatitis B surface antigen (HBsAg) for delivery in the colon, which provided prolonged immunization against the Hepatitis B infection. In this study, MPLA was the adjuvant; it activated toll-like receptor type 4 (TLR 4) and Hbs Ag that act as the antigens to be delivered, and thus enabled the simultaneous delivery of both adjuvant and antigens inside the colon. The results indicated that it was effective in the generation of humoral and cellular immune responses [23] . Stimulator of interferon gene (STING) is a prominent agonist which stimulates cyclic dinucleotides (CDNs) to activate IRF3 and NFκB pathways and secrete various pro-inflammatory cytokines. Jack Hu et al. had developed pH sensitive capsid-like hollow polymeric nanoparticle loaded with STING agonist, cyclic diguanylate monophosphate (cdGMP), as a Middle East respiratory syndrome coronavirus (MERS-CoV) vaccine. Delivery of both STING agonist and MERS-CoV receptor binding domain antigen in the surface of the nanoparticle mimicked as virus-liked nanoparticle and induced Th1 type immune response which is a prominent vaccine against the infection [94] .