Immune Response of A Novel ATR-AP205-001 Conjugate Anti-hypertensive Vaccine

Abstract

We developed a virus-like particle (VLP)-based therapeutic vaccine against angiotensin II receptor type 1, ATR-AP205-001, which could significantly reduce the blood pressure and protect target organs of hypertensive animals. In this study, we focused on the immunological effect and safety of the VLP-based vaccine. By comparing to the depolymerized dimeric vaccine ATR-Dimer-001, we found that ATR-AP205-001 reached subcapsular sinus of lymph node shortly after administration, followed by accumulation on follicle dendritic cells via follicle B cell transportation, while ATR-Dimer-001 vaccine showed no association with FDCs. ATR-AP205-001 vaccine strongly activated dendritic cells, which promoted T cells differentiation to follicular helper T cells. ATR-AP205-001 vaccine induced powerful germinal center reaction, which was translated to a boost of specific antibody production and long-lasting B cell memory, far superior to ATR-Dimer-001 vaccine. Moreover, neither cytotoxic T cells, nor Th1/Th17 cell-mediated inflammation was observed in ATR-AP205-001 vaccine, similar to ATR-Dimer-001 vaccine. We concluded that ATR-AP205-001 vaccine quickly induced potent humoral immunity through collaboration of B cells, follicular dendritic cells and follicular helper T cells, providing an effective and safe intervention for hypertension in the future clinical application.

Development of Spike Receptor-Binding Domain Nanoparticles as a Vaccine Candidate against SARS-CoV-2 Infection in Ferrets

“…The efficacy of these nanoparticle-engineered vaccines exceeds that of traditional vaccines, such as whole inactivated vaccines of bacterial and viral pathogens (34)(35)(36)(37)(38). Moreover, recent studies have shed light on the immunological advantages of nanoparticle-based vaccines in nearly every step of humoral and cellular immunity: efficient antigen transport to draining lymph nodes and antigen presentation by follicular dendritic and helper T cells, as well as high levels of activation of the germinal centers (30,39,40). Among the genetically engineered nanoparticles, ferritin is the most well characterized in the bionanotechnology field.…”

A bivalent antihypertensive vaccine targeting L‐type calcium channels and angiotensin AT1 receptors

“…However, in most cases, the epitopes conjugated with the carrier VLPs are not capable of blocking epitopes of the carrier protein effectively, and large numbers of the epitopes of the carrier protein are exposed to the lymphocytes which recognize them. As a result, the conjugated vaccines induce dominant antibodies against the carrier protein instead of the conjugated peptide epitopes (Hu et al, ), which may impair the humoral immune response against the conjugated epitopes. HBcAg VLPs have been studied intensively and used as epitope carriers in previous clinical trials (Gregson et al, ; Nardin et al, ; Oliveira et al, ).…”

“…In the patch‐clamp experiments, group sizes were selected on the basis of a previous study indicating that n = 6 per group may provide sufficient power for detecting the activities of L‐type calcium channel (Liao et al, ). In the immunological studies, group sizes were selected on the basis of another study indicating that n = 6 may be sufficient for study of immune responses induced by vaccination (Hu et al, ). All the group sizes indicate the number of independent values, and the statistical analysis used these independent values.…”

Development of spike receptor-binding domain nanoparticle as a vaccine candidate against SARS-CoV-2 infection in ferrets

“…The efficacy of these nanoparticle-engineered vaccines outperforms traditional vaccines, such as whole inactivated vaccines of bacterial and viral pathogens (34)(35)(36)(37)(38). Moreover, recent studies have shed light on the immunological advantages of nanoparticle-based vaccines in nearly every step of the humoral and cellular immunity: efficient antigen transport to draining lymph nodes, antigen presentation by follicular dendritic and helper T cells, as well as high level of activation of the germinal centers (30,39,40). Among the genetically engineered nanoparticles, ferritin is the most well-characterized in the bionanotechnology field.…”