In Vivo Imaging Tracking and Immune Responses to Nanovaccines Involving Combined Antigen Nanoparticles with a Programmed Delivery

Abstract

Combined nanovaccine can generate robust and persistent antigen-specific immune responses. A combined nanovaccine was developed based on antigen-loaded genipin-cross-linked-polyethyleneimine-antigen nanoparticles and in vivo multispectral fluorescence imaging tracked the antigen delivery of combined nanovaccine. The inner layer antigen nanoparticles carried abundant antigens by self-cross-linking for persistent immune response, whereas the outer antigen on the surface of antigen nanoparticles provided the initial antigen exposure. The delivery of combined nanovaccine was tracked dynamically and objectively by the separation of inner genipin cross-linked antigen nanoparticle and the outer fluorescent antigen. The immune responses of the combined nanovaccine were evaluated including antigen-specific CD4 and CD8 T-cell responses, IgG antibody level, immunological memory, and CD8 cytotoxic T lymphocyte responses. The results indicated that the inner and outer antigens of combined vaccine can be tracked in real time with a programmed delivery by the dual fluorescence imaging. The programmed delivery of the inner and outer antigens induced strong immune responses with a combination of a quick delivery and a persistent delivery. With adequate antigen exposure, the dendritic cells were effectively activated and matured, and following T cells were further activated for immune response. Compared with a single nanoparticle formulation, the combined nanovaccine exactly elicited a stronger antigen-specific immune response.

Artificial Metalloprotein Nanoanalogues: In Situ Catalytic Production of Oxygen to Enhance Photoimmunotherapeutic Inhibition of Primary and Abscopal Tumor Growth

“…APCs capture antigens and migrate into the lymph nodes and spleen. [ 41 ] Subsequently, these cells present antigenic peptides to the T cells, which triggers the abscopal effect of adaptive immune responses with the help of costimulatory molecules. [ 42 ] Among these T cells, the cytotoxic T lymphocytes (CTLs, CD3 + CD4 − CD8 + ) can kill cancer cells, and helper T cells (CD3 + CD4 + CD8 − ) play a vital role in regulating the immune response.…”

Recent Advances in Polymeric Nanomedicines for Cancer Immunotherapy

“…In addition, antigen release profile can be modulated by using combined nanovaccine system which can provide both a persistent immunity through the sustained release of antigen and a robust original immunity by abundant antigen exposure . These two types of release manners of combined nanovaccine can induce the activation of DCs as well as the T cell differentiation in lymph nodes, eliciting stronger antigen‐specific immune responses compared to single nanovaccine or free antigen.…”

“…These two types of release manners of combined nanovaccine can induce the activation of DCs as well as the T cell differentiation in lymph nodes, eliciting stronger antigen‐specific immune responses compared to single nanovaccine or free antigen. [86b,c] To induce a robust and persistent immune responses, Dong et al have developed a combined nanovaccine containing inner and outer antigens, which can be tracked simultaneously by in vivo multispectral fluorescence imaging. [86a] Compared with free antigen or antigen‐adsorbed nanoparticles, the combined nanovaccine can induce higher antigen‐specific immune response.…”

“…[86b,c] To induce a robust and persistent immune responses, Dong et al have developed a combined nanovaccine containing inner and outer antigens, which can be tracked simultaneously by in vivo multispectral fluorescence imaging. [86a] Compared with free antigen or antigen‐adsorbed nanoparticles, the combined nanovaccine can induce higher antigen‐specific immune response. In order to investigate the programmed delivery of the nanovaccines, fluorescence imaging was utilized because it is noninvasive and can offer real‐time tracking, low radiation, and high sensitivity .…”

“…[123c,126] In any nanoparticle‐based vaccine for cancer immunotherapy that includes antigens and adjuvants in its delivery system, effective, sustained and prolonged antigen or adjuvant release is crucial for the activation and maturation of DCs as described in Section . [79,83,86a,b,127] Moreover, to achieve efficient cancer immunotherapy with vaccines, the cytosolic antigen or adjuvant must be released from the delivery vectors and efficient DC migration to the lymph nodes must be ensured to guarantee that the naïve T lymphocytes will be primed and activated.…”