Dataset Information

HRSV prefusion-F protein with Adju-Phos adjuvant induces long-lasting Th2-biased immunity in mice.

ABSTRACT: The development of human respiratory syncytial virus (hRSV) vaccine has been hampered by the risk of enhanced respiratory disease (ERD) which was induced by highly skewed toward Th2 immune response. In our previous study, we expressed the recombinant pre-F protein using Escherichia coli BL21, called RBF. To verify if the RBF protein could cause ERD, we tested the immunogenicity and safety of RBF with a commercial alum adjuvant (GMP-grade Adju-Phos). RBF alone and RBF/Adju-Phos elicited long-lasting protective antibodies and a cellular immune response in mice after three immunizations. Unfortunately, compared with the mice in RBF group, mice in RBF/Adju-Phos generated a serious Th2 humoral immune response that elicited Th2-mediated lung pathology. From the IL-4+:IFNγ+ ratio, there was also a robust Th2 cellullar immunologic response in the RBF/Adju-Phos group. This study demonstrates that it may not be enough for RBF to increase the titer of neutralizing antibodies. A balanced immune response must be induced for hRSV vaccine safety.

SUBMITTER: Li H

PROVIDER: S-EPMC8803181 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

HRSV prefusion-F protein with Adju-Phos adjuvant induces long-lasting Th2-biased immunity in mice.

Li Hai H Ren Hu H Zhou Yangzi Y Zhang Yan Y Cao Lei L Xu Wenbo W

PloS one 20220131 1

The development of human respiratory syncytial virus (hRSV) vaccine has been hampered by the risk of enhanced respiratory disease (ERD) which was induced by highly skewed toward Th2 immune response. In our previous study, we expressed the recombinant pre-F protein using Escherichia coli BL21, called RBF. To verify if the RBF protein could cause ERD, we tested the immunogenicity and safety of RBF with a commercial alum adjuvant (GMP-grade Adju-Phos). RBF alone and RBF/Adju-Phos elicited long-last ...[more]

PMID: 35100303

Similar Datasets

Project description:Innate immune memory describes the functional reprogramming of innate immune cells after pathogen contact, leading to either a boosted (trained immunity) or a diminished (immune tolerance) response to a secondary stimulus. Immune tolerance or "sepsis-induced immunosuppression" is a typical hallmark of patients after sepsis survival, characterized by hypo-responsiveness of the host's immune system. This condition renders the host vulnerable for a persisting infection or the occurrence of secondary, often opportunistic infections, along with an increased mortality rate. The mechanisms involved in the maintenance of this long-lasting condition are not examined yet. Polymicrobial abdominal sepsis was induced in 12 week old male C57BL/6 mice by cecal ligation and puncture. Mice were euthanized 3 months after insult. Immune cell composition of the spleen and whole blood, as well as stem and progenitor cells of the bone marrow, were assessed by flow cytometry. Whole blood and bone marrow monocytes were stimulated with LPS and supernatant levels of TNF and IL-6 detected by ELISA. Furthermore, naïve bone marrow monocytes were analyzed for metabolic (Seahorse technology) and transcriptomic (RNA sequencing) changes. Flow cytometric analysis revealed an increase of inflammatory monocytes and regulatory T cells in the spleen, whereby immune composition of whole blood kept unchanged. Granulocyte-monocyte progenitor cells are increased in sepsis survivors. Systemic cytokine response was unchanged after LPS challenge. In contrast, cytokine response of post-septic naïve bone marrow monocytes was increased. Metabolic analysis revealed enhanced glycolytic activity, whereas mitochondrial indices were not affected. In addition, RNA sequencing analysis of global gene expression in monocytes revealed a sustained signature of 367 differentially expressed genes. We here demonstrate that sepsis via functional reprogramming of naïve bone marrow monocytes induces a cellular state of trained immunity, which might be counteracted depending on the compartmental localization of the cell. These findings shed new light on the complex aftermath of sepsis and open up a new pathophysiological framework in need for further research.

Dataset Information

HRSV prefusion-F protein with Adju-Phos adjuvant induces long-lasting Th2-biased immunity in mice.

Publications

HRSV prefusion-F protein with Adju-Phos adjuvant induces long-lasting Th2-biased immunity in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets