Dataset Information

Novel Peptide-Based PD1 Immunomodulators Demonstrate Efficacy in Infectious Disease Vaccines and Therapeutics.

ABSTRACT: Many pathogens use the same immune evasion mechanisms as cancer cells. Patients with chronic infections have elevated levels of checkpoint receptors (e.g., programed cell death 1, PD1) on T cells. Monoclonal antibody (mAb)-based inhibitors to checkpoint receptors have also been shown to enhance T-cell responses in models of chronic infection. Therefore, inhibitors have the potential to act as a vaccine "adjuvant" by facilitating the expansion of vaccine antigen-specific T-cell repertoires. Here, we report the discovery and characterization of a peptide-based class of PD1 checkpoint inhibitors, which have a potent adaptive immunity adjuvant capability for vaccines against infectious diseases. Briefly, after identifying peptides that bind to the recombinant human PD1, we screened for in vitro efficacy in reporter assays and human peripheral blood mononuclear cells (PBMC) readouts. We first found the baseline in vivo performance of the peptides in a standard mouse oncology model that demonstrated equivalent efficacy compared to mAbs against the PD1 checkpoint. Subsequently, two strategies were used to demonstrate the utility of our peptides in infectious disease indications: (1) as a therapeutic in a bacteria-induced lethal sepsis model in which our peptides were found to increase survival with enhanced bacterial clearance and increased macrophage function; and (2) as an adjuvant in combination with a prophylactic malaria vaccine in which our peptides increased T-cell immunogenicity and the protective efficacy of the vaccine. Therefore, our peptides are promising as both a therapeutic agent and a vaccine adjuvant for infectious disease with a potentially safer and more cost-effective target product profile compared to mAbs. These findings are essential for deploying a new immunomodulatory regimen in infectious disease primary and clinical care settings.

SUBMITTER: Kotraiah V

PROVIDER: S-EPMC7068811 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Novel Peptide-Based PD1 Immunomodulators Demonstrate Efficacy in Infectious Disease Vaccines and Therapeutics.

Kotraiah Vinayaka V Phares Timothy W TW Browne Cecille D CD Pannucci James J Mansour Marc M Noe Amy R AR Tucker Kenneth D KD Christen Jayne M JM Reed Charles C MacKay Alecia A Weir Genevieve M GM Rajagopalan Rajkannan R Stanford Marianne M MM Chung Chun-Shiang CS Ayala Alfred A Huang Jing J Tsuji Moriya M Gutierrez Gabriel M GM

Frontiers in immunology 20200306

Many pathogens use the same immune evasion mechanisms as cancer cells. Patients with chronic infections have elevated levels of checkpoint receptors (e.g., programed cell death 1, PD1) on T cells. Monoclonal antibody (mAb)-based inhibitors to checkpoint receptors have also been shown to enhance T-cell responses in models of chronic infection. Therefore, inhibitors have the potential to act as a vaccine "adjuvant" by facilitating the expansion of vaccine antigen-specific T-cell repertoires. Here, ...[more]

PMID: 32210956

Similar Datasets

Project description:Infectious bronchitis virus (IBV) has been frequently reported in chickens worldwide, including in the Eastern Region of Saudi Arabia (ERS). Several IBV outbreaks were recently reported in chickens despite the massive use of various vaccines. Based on partial sequencing of the S1 gene, at least three genotypes were reported (CK/CH/LDL/97I, IS/720/99, and IS/Variant2/98) in the ERS with no available homologous vaccines. Herein, we tried to evaluate the protection provided by some selected commercial-available vaccines against these three genotypes. We divided the experimental chickens into eight groups. Representative isolates from these genotypes were inoculated into three groups of broiler chickens vaccinated with the H-120 vaccine at the age of 1 day and boosted with the 4/91 vaccine at the age of 14 days (challenged groups). One group of chickens had received the same protocol of IBV vaccines but was kept without infection to serve as a vaccine control group. The three isolates were inoculated into three other similar but unvaccinated groups of broiler chickens (infected groups). Group eight chickens were neither vaccinated nor infected and used as a negative control group. Evaluation of the protection induced by the tested vaccination schedule was assessed by several criteria, including the ability to reduce the severe clinical signs caused by IBV infection, changes in the body temperature of various groups of chickens, the reduction in the magnitude of IBV-induced lesions, and the reduction in the viral loads in tracheas of a different group of chicken. Monitoring the immune status of chickens was also recorded based on the hemagglutination inhibition antibodies in sera of various groups of chickens. Our results show clinical and tracheal protection against IBV/IS/Variant2/98-like and IBV/IS/720/99-like strains. Moderate protection was observed in the IBV/CK/CH/LDL/97I-like pressure. The kidneys of the challenged groups of chickens showed minimal or no gross lesions compared with the infected groups, even in those chickens challenged with the IBV/CK/CH/LDL/97I-like strain. In conclusion, this is the first study to perform the protectotyping of some IBV strains from Saudi Arabia. It demonstrated the proficiency of the investigated vaccination schedule in control of infection of broiler chickens with IBV/IS/Variant2/98 and IBV/IS/720/99 strains. It is highly recommended to introduce the homologous IBV/CK/CH/LDL/97I-based vaccine to the vaccination protocols of chickens in the ERS to match the circulating strains and ensure better protection.

Dataset Information

Novel Peptide-Based PD1 Immunomodulators Demonstrate Efficacy in Infectious Disease Vaccines and Therapeutics.

Publications

Novel Peptide-Based PD1 Immunomodulators Demonstrate Efficacy in Infectious Disease Vaccines and Therapeutics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets