Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials

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

Highly active antiretroviral therapy (HAART) is a prominent strategy for the treatment of acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV). Nanovaccines, such as nanocapsules, nanocrystals, lipid NPs, nanocarriers, liposomes, and micelles, have been recently investigated for anti-HIV therapies. Although many anti-retroviral drugs are available for treatment, none of them can eradicate the viral reservoir [104] . Engineered biomimetic nanovaccines have adverse properties in modulating our immune system against viral infection. They show high encapsulation efficiency of anti-retroviral drugs, cytokines, and enzymes and site-specific drug releases [105] . Liposomes are endocytosed through mononuclear phagocytic system cells (MPS), and reach the HIV-infected reservoir [106] . The liposomal delivery of anti-HIV vaccines was investigated to induce antibody and cellular immune responses 25 years ago [107] . The formulation of the liposomal vaccine with IL-7 immune stimulator and recombinant HIV envelope protein (env-2-3SF2) as an antigen showed a strong antibody response, compared to liposomal delivery with IL-7 or the liposome alone. When pathogen-free mice were vaccinated with env-2-3SF2 and IL-7, the antibody production and CTL activity were significantly increased [107] . Hanson et al. [108] investigated the liposomal delivery of membrane-proximal external region (MPER) with a suitable antigen, monophosphoryl lipid-A (MPLA), and the stimulator of interferon gene (STING) agonist cyclic-di-GMP (cdGMP) as an active HIV vaccine. The administration of the liposomal vaccine with MPER, molecular adjuvants MPLA and cdGMP achieved a significant humoral response, as well as T-cell responses [108] . Andersson et al. [109] developed HIV VLPs composed of HIV env antigen HIV BaL gp120/gp41, which is a viral surface glycoprotein that targets HIV-1 and TLR ligands. These HIV VLPs vaccines modulate the immune system and maintain the germinal center from B-cell hypermutation. Preservation of the germinal center results in the secretion of high HIV neutralizing antibodies. VLPs, like nanovaccines composed of antigen and different TLR ligands, such as TLR2 (PAM3CAG), TLR3 (dsRNA), TLR4 (MPLA), or TLR7/8 (resiquimod), can accelerate the immunogenicity of mice. This combined nanovaccine induced Th-1 like cytokines, and prolonged the lymph node germinal center and T follicular cells for antibody production [109] . Intranasal immunization of the HIV VLP nanovaccine for 12 weeks reduced the env-specific IgG1 titers. However, IgG2b, IgG2c, and IgG3 titers were well maintained during the study, which is the main factor for generating a neutralizing antibody against HIV. The combination of both antigens and adjuvants with VLPs showed a robust immune response and well-maintained germinal center. VLPs encoded with the HIV-1 adenovirus primed immunogen is an effective strategy towards HIV vaccination. The envelope glycoprotein (Env) is an antibody-inducing prophylactic drug presented on the HIV-1 particle. VLPs encoded with docked HIV-1 consensus Env antigen produced the antibody response, and released more neutralizing antibodies against HIV [110] . The ectodomain protein, gp140, has been investigated recently as an alternate Env targeting for induction of neutralizing antibodies against HIV [111] . Delivery of lipid nanocapsule modified with trimeric gp140 (gp140T) on the surface had promoted a strong antibody response and tim