Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials

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

Malaria is a ubiquitous parasite disease found worldwide and is caused by protozoan parasites. The current treatment for malaria involves the oral administration of the traditional antimalaria drugs, such as chloroquine, pyrimethamine, artesunate, and sulfadoxine. But the potency of these drugs is diminished by the drug resistance ability of these parasites. The downside of the current treatments for malaria includes low stability in the stomach, higher side effects, and low half-life inside the body [114] . Nanovaccines are the best alternatives to combat this parasite disease. Nanocarriers can carry active drugs to specific sites with minimal loss and side effects for adverse therapeutic effects [114] . Biomimetic nanocarriers, such as liposomes and proteins, are highly biocompatible and promising for the drug delivery application [115] . Malaria vaccines are less resistant against recombinant antigens and require repeated re-boosting. Liposomes are a well-known drug carrier that can deliver the drug within the host without degradation [116] . The surface modification of a liposome with the targeting ligands and antibodies can precisely bind to the infected cells and facilitates site-specific drug delivery. Marques et al. [117] reported that heparin-coated liposomes, loaded with primaquine, had an adverse antimalarial activity. Due to the higher binding affinity of the heparin towards the heparin-binding protein in the infected erythrocyte cell membrane surface, it delivered the drug to infected sites. Immunoliposome (ILP), a liposome modified to target the immune system, has been recently investigated for antimalarial activity to target plasmodium-infected red blood cells (pRBC) [118] . Liposomes modified with glycosaminoglycan chondroitin 4-sulfate (a heparin substitute) for the delivery of primaquine have shown an additive effect compared to the control [119] . Plasmodium falciparum erythrocyte membrane protein 1, the primary receptor for chondroitin-4 sulfate, is a parasite-mediated antigen that is present in the endothelium of postcapillary venule. It enhances the adhesion of the liposomes towards pRBC [119] . Rajeev et al. [120] reported an antimalaria vaccine by liposomal delivery of merozoite surface protein (MSP-1) which is presented on the surface of Plasmodium falciparum. The transcutaneous injection of this antigen accelerated immune responses by activating epidermal antigen-presenting cells. The liposomal delivery of membrane antigen induces strong humoral and cell-mediated immune responses [120] . Labdhi et al. [121] developed a self-assembled protein nanovaccine delivery with adjuvant-based liposomes to target Plasmodium falciparum. The self-assembled protein NP contained 60-identical monomer protein chains comprised of P. falciparum Circumsporozoite Protein (Pf CSP), CD 4+, CD 8+, and T H epitopes for inducing immune responses. Adjuvant-augmented (QS21, alhydrogel) liposomal delivery of the self-assembled protein nanovaccine targeted the native Pf CSP and stimulated the immune responses, with 80% or more mice gaining complete protection from malaria [121] . The delivery of two antimalarial drugs, such as lipophilic aminoquinolines and amino alcohol derivative encapsulated into ILP, had more than 90% encapsulation efficiency through a citrate buffered pH gradient method. The ILPs performed in vivo RBC targeting, showed higher retention time, and reduced malaria parasite densities in blood, compared to the non-targeted d