Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA

Abstract

The importance of a balanced TH1/TH2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints are involved in the induction of adoptive immunity and their inhibitors (monoclonal antibodies) are licensed for cancer therapy, we investigated the effect of checkpoint blockade after HIV-1 genetic vaccination on enhancement and modulation of antiviral antibody responses. By intraperitoneal administration of checkpoint antibodies in mice we observed an induction of anti-drug antibodies which may interfere with immunomodulation by checkpoint inhibitors. Therefore, we blocked immune checkpoints locally by co-electroporation of DNA vaccines encoding the active soluble ectodomains of programmed cell death protein-1 (PD-1) or its ligand (PD-L1), respectively. Plasmid-encoded immune checkpoints did not elicit a detectable antibody response, suggesting no interference with their immunomodulatory effects. Co-electroporation of a HIV-1 DNA vaccine formulation with soluble PD-L1 ectodomain increased HIV-1 Env-specific TH1 CD4 T cell and IgG2a antibody responses. The overall antibody response was hereby shifted towards a more TH1/TH2 balanced subtype pattern. These findings indicate that co-electroporation of soluble checkpoint ectodomains together with DNA-based vaccines has modulatory effects on vaccine-induced immune responses that could improve vaccine efficacies.

CD4+ T Cells Induced by Tuberculosis Subunit Vaccine H1 Can Improve the HIV-1 Env Humoral Response by Intrastructural Help

“…Serum was transferred into clean tubes and stored at −20 °C until further use. Env-specific antibody levels in the serum were determined by gp120 ELISA as previously described [ 36 ]. Briefly, 96 well high-binding microtiter plates were coated with 100 ng of ConBgp120-His in 100 µL bicarbonate buffer (pH 9.6) per well at room temperature overnight.…”

The Use of Nanobiotechnology in Immunology and Vaccination

“…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 ]. A new strategy in vaccine design is to target B-cells by derivatizing the nanoparticle carrier with TLR ligands [ 53 ].…”

T Cell Immunity against Influenza: The Long Way from Animal Models Towards a Real-Life Universal Flu Vaccine

“…First, an increased number of initial TRMs could lead to longer maintenance of the protective levels of T cell immunity. The co-delivery of inflammatory factors in genetic vaccinations has been used extensively to modulate systemic immune responses [ 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 ]. We could show that the mucosal co-delivery of interleukin (IL)-1β can increase the induction of lung CD4 + and CD8 + TRMs significantly [ 73 ], thus illustrating that genetic adjuvants might be an important tool to boost TRM responses.…”