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Helicobacter pylori Neutrophil-Activating Protein (HP-NAP) is a major virulence factor and a highly conserved member of the ferritin-like protein family, typically structured as a 150 kDa dodecameric complex [8], [14]. Its primary biological function involves the recruitment and activation of host immune cells, specifically neutrophils and monocytes, through interactions with Toll-like receptor 2 (TLR2) and a pertussis toxin-sensitive G protein-coupled receptor [1], [2]. This activation triggers an oxidative burst and the release of pro-inflammatory cytokines, which drive the chronic inflammation, tissue damage, and oxidative stress characteristic of H. pylori-associated gastritis, peptic ulcers, and gastric adenocarcinoma [2], [12]. Inside the bacterium, HP-NAP also functions as a Dps-like protein that sequesters iron and protects bacterial DNA from oxidative damage [8]. In clinical development, HP-NAP is a key target for H. pylori vaccines designed to neutralize its pathogenic activity and prevent bacterial colonization [10], [12]. Furthermore, its potent ability to induce Th1-type immune responses has led to its exploration as an immunotherapeutic agent, such as an adjuvant in cancer vaccines or as a cargo in oncolytic viruses like MV-s-NAP to boost anti-tumor immunity and redirect allergic Th2 responses [4], [6], [10].
Neutralization of protein activity by antibodies or vaccines inhibits neutrophil recruitment and activation to reduce mucosal inflammation; therapeutic delivery via oncolytic viruses induces local innate immune activation and systemic anti-tumor Th1 immune responses.
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