Summary: A new study identifies a bacterial protein that enhances vaccine responses and may help the immune system target diseases such as cancer.
Source: Boston University Medical Center
Protein PorB Boosts Vaccine Effectiveness and Expands Immune Protection
Researchers at Boston University School of Medicine (BUSM) report that a protein derived from the outer membrane of Neisseria meningitidis, called PorB, acts as a powerful vaccine adjuvant. The team purified PorB and combined it with vaccine antigens in experimental models, producing a stronger and broader immune response than antigen alone. The findings, published in Scientific Reports, clarify how certain adjuvants work and suggest new ways to improve vaccines against infectious diseases and potentially non-infectious diseases such as cancer.
Unlike many adjuvants that primarily increase antibody production, PorB has the capacity to both enhance antibody responses and stimulate cytotoxic T cells—immune cells that can directly destroy infected or transformed cells. In controlled comparisons, the group receiving antigen mixed with PorB demonstrated increased numbers of activated immune cells within draining lymph nodes and a higher production of cytotoxic T cells than the group given antigen alone.
“This study deepens the general understanding of how vaccine adjuvants modulate immune responses,” said Lee Wetzler, MD, professor of medicine and microbiology at BUSM and corresponding author of the study. “Formulating antigen with PorB triggers a cascade of cellular events at the site of injection and within lymphoid tissues that are critical for establishing protection against a broad array of infectious diseases—and potentially for diseases such as cancer.”
How PorB Works: TLR2 Binding, APC Trafficking, and Cross-presentation
The researchers describe PorB as a naturally occurring ligand for Toll-like receptor 2 (TLR2). TLR ligands are known to activate both innate and adaptive immune responses while shaping how immune cells respond to antigens. In laboratory assays using bone marrow–derived dendritic cells (BMDCs) and in vivo experiments, PorB increased the level of antigen retained in endosomal and lysosomal compartments of antigen-presenting cells (APCs). This retention enhanced APC trafficking to draining lymph nodes and improved antigen cross-presentation—the process by which APCs display extracellular antigens on MHC class I molecules to prime CD8+ cytotoxic T cells.
By promoting both APC recruitment to secondary lymphoid tissues and more efficient cross-presentation, PorB expands the range of adjuvant effects beyond simple antibody boosting. The result is an antigen-specific T cell response that is more robust, with greater activation and effector function of cytotoxic T cells in models that received the PorB-adjuvanted vaccine.
Implications for Vaccines and Disease Targets
The dual ability of PorB to enhance antibody production and stimulate cytotoxic T cell responses makes it a promising candidate for vaccine strategies that require cellular immunity in addition to humoral immunity. Such strategies are important not only for combating bacterial and viral infections but also for therapeutic vaccines aimed at cancer or other diseases where targeted cellular responses are desirable. According to the authors, adjuvants like PorB that target TLR pathways may help the immune system identify and eliminate abnormal or infected cells before disease becomes established.
Funding: This research was supported by the National Institutes of Health (grant AI040944).
Source: Gina DiGravio, Boston University Medical Center
Image source: NeuroscienceNews.com image used for illustrative purposes only.
Original research: “The TLR2 Binding Neisserial Porin PorB Enhances Antigen Presenting Cell Trafficking and Cross-presentation” by Michael L. Reiser, Munir M. Mosaheb, Christina Lisk, Andrew Platt & Lee M. Wetzler, published in Scientific Reports (published online April 7, 2017). doi:10.1038/s41598-017-00555-4
Abstract (concise)
TLR ligands modulate both innate and adaptive immune cells and influence cellular immune responses. The outer membrane protein PorB from Neisseria meningitidis is a natural TLR2 ligand and functions as an adjuvant. In this study, PorB increased antigen levels in endo-/lysosomal compartments of BMDCs, enhanced APC trafficking to draining lymph nodes, and promoted antigen cross-presentation. PorB efficiently stimulated antigen-specific T cell responses in vitro and in vivo, expanding the known adjuvant activities to include enhanced cross-presentation and increased APC recruitment to secondary lymphoid tissues. These findings contribute to a better understanding of how TLR-ligand–based adjuvants can shape and improve immune responses.