Developing a safe and effective malaria vaccine is critical to reducing the spread and resurgence of this deadly disease, especially in children. In recent years, vaccine technology has seen expanded development of subunit protein, peptide, and nucleic acid vaccines. This is due to their inherent safety, the ability to tailor their immune response, simple storage requirements, easier production, and lower expense compared to using attenuated and inactivated organism-based approaches. However, these new vaccine technologies generally have low efficacy. Subunit vaccines, due to their weak immunogenicity, often necessitate advanced delivery vectors and/or the use of adjuvants. A new area of vaccine development involves design of synthetic micro- and nano-particles and adjuvants that can stimulate immune cells directly through their physical and chemical properties. Further, the unique and complex life cycle of the Plasmodium organism, with multiple stages and varying epitopes/antigens presented by the parasite, is another challenge for malaria vaccine development. Targeting multistage antigens simultaneously is therefore critical for an effective malaria vaccine. Here, we rationally design a layer-by-layer (LbL) antigen delivery platform (we called LbL NP) specifically engineered for malaria vaccines. A biocompatible modified chitosan nanoparticle (trimethyl chitosan, TMC) was synthesized and utilized for LbL loading and release of multiple malaria antigens from pre-erythrocytic and erythrocytic stages. LbL NP served as antigen/protein delivery vehicles and were demonstrated to induce the highest Plasmodium falciparum Circumsporozoite Protein (PfCSP) specific T-cell responses in mice studies as compared to multiple controls. From immunogenicity studies, it was concluded that two doses of intramuscular injection with a longer interval (4 weeks) than traditional malaria vaccine candidate dosing would be the vaccination potential for LbL NP vaccine candidates. Furthermore, in PfCSP/Py parasite challenge studies we demonstrated protective efficacy using LbL NP. These LbL NP provided a significant adjuvant effect since they may induce innate immune response that led to a potent adaptive immunity to mediate non-specific anti-malarial effect. Most importantly, the delivery of CSP full-length protein stimulated long-lasting protective immune responses even after the booster immunization 4 weeks later in mice.

or subcutaneously. However, they do not elicit a sufficient local immune response, [1] such as the induction of immuno globulin A (IgA), which is important to effectively prevent HIV-1 infection. [2] Instead, a mucosal vaccine offers several advantages including noninvasive application, elicitation of both systemic and mucosal immune responses, and compatibility with multiple booster immunizations, all of which amplify the effectiveness of the vaccine and thereby provide better protection from viral infection. [3] More importantly, mucosal vaccination targets specific mucosal sites, such as nasal, oral, and vaginal tissue, and induces frontline immunity at the site of HIV-1 entry which can prevent the establishment and dissemination of an infection. As for induction of appropriate responses to HIV-1 at the most common sites of infection, intranasal administration has been shown to be one of the most effective routes for mucosal immunization among the various methods tested. [4] Vaccines delivered by the nasal route can also generate antibodies in the rectum and genital tract. As a result, the identification of safe adjuvants for nasally administered Env proteins could have a large impact on future HIV vaccine development. [5] HIV-1 entry is first mediated by molecular recognition between the viral glycoprotein (gp)120 and its receptor CD4 on host T-cells. As a key antigen that can be targeted by neutralizing antibodies (NAbs), gp120 has been the focus of extensive structural property studies to investigate its use as a vaccine candidate. However, the problem with the use of pure recombinant or synthetic glycoproteins in HIV-1 vaccines is that they are generally far less immunogenic than live or inactivated whole organism vaccines. Therefore, there is significant need for an HIV-1 antigen delivery platform or adjuvant to enhance delivery efficiency of recombinant antigen, but also maintain certain conformations of immunogens to preserve epitopes of broadly NAbs as the potential vaccine. This approach can reduce the amount of immunogen and the number of immunizations needed for protective immunity. It will also serve to improve the uptake of antigens by the mucosal antigen presenting cells (APCs) and enhance the interaction between mucosa and antigens. [6] The human immunodeficiency virus (HIV-1) envelope glycoprotein spike is targeted by antibodies and therefore represents the main viral antigen for antibody-based vaccine design. One of the challenges in HIV-1 vaccine development is inducing efficient immune system recognition and response to the virus without establishing an infection. Since HIV-1 enters the body at mucosal surfaces, induction of immune response at these sites is a preferred preventive approach. Nasal administration is an effective route for mucosal immunization since it can stimulate immune responses both locally and distantly. In this paper, Luna Labs develops a short carbon nanotube-based delivery platform known as "CNTVac." The size of carbon nanotubes is controlled to possess HIV-1 particle-...