Calcium Phosphate Nanoparticle-Based Vaccines as a Platform for Improvement of HIV-1 Env Antibody Responses by Intrastructural Help

Abstract

Incorporation of immunodominant T-helper epitopes of licensed vaccines into virus-like particles (VLP) allows to harness T-helper cells induced by the licensed vaccines to provide intrastructural help (ISH) for B-cell responses against the surface proteins of the VLPs. To explore whether ISH could also improve antibody responses to calcium phosphate (CaP) nanoparticle vaccines we loaded the nanoparticle core with a universal T-helper epitope of Tetanus toxoid (p30) and functionalized the surface of CaP nanoparticles with stabilized trimers of the HIV-1 envelope (Env) resulting in Env-CaP-p30 nanoparticles. In contrast to soluble Env trimers, Env containing CaP nanoparticles induced activation of naïve Env-specific B-cells in vitro. Mice previously vaccinated against Tetanus raised stronger humoral immune responses against Env after immunization with Env-CaP-p30 than mice not vaccinated against Tetanus. The enhancing effect of ISH on anti-Env antibody levels was not attended with increased Env-specific IFN-γ CD4 T-cell responses that otherwise may potentially influence the susceptibility to HIV-1 infection. Thus, CaP nanoparticles functionalized with stabilized HIV-1 Env trimers and heterologous T-helper epitopes are able to recruit heterologous T-helper cells induced by a licensed vaccine and improve anti-Env antibody responses by intrastructural help.

The Use of Nanobiotechnology in Immunology and Vaccination

“…In addition to the above nanostructures, researchers are testing other intelligent nanostructures for use in vaccines and immunology. For example, calcium phosphate or hydroxyapatite nanoparticles can be a good platform for vaccination [ 50 ]. Specialized nano-platforms can also be made using plasmids and DNA technology [ 51 , 52 ].…”

Conjugation of Native-Like HIV-1 Envelope Trimers onto Liposomes Using EDC/Sulfo-NHS Chemistry: Requirements and Limitations

“…First steps towards the development of liposome-based vaccines capable of harnessing intrastructural help date back to the early 1990′s [ 61 , 62 , 63 ]. Recent studies that involved particle-based vaccines (virus-like particles and calcium phosphate nanoparticles) have provided additional proof of concept for this type of strategy within the context of HIV-1 [ 64 , 65 , 66 , 67 , 68 ]. Recent independent reports on liposome-based vaccines (against HIV-1, malaria, group A streptococci and ErbB-2 overexpressing breast cancer) utilizing the same principle are also very encouraging [ 69 , 70 , 71 , 72 ].…”

Nano vaccines and nano materials for vaccines

“…DCs中的自噬途径而产生显著增强的T细胞免疫应 答 [87] . 磷酸钙纳米颗粒作为免疫佐剂的效力已经在各 种疫苗制剂中得到证实, 能够传递多肽、核酸等多种 抗原, 并且临床试验也证实了其安全性 [12,61] .…”