Meningococcal factor H binding protein as immune evasion factor and vaccine antigen

Principato, Silvia; Pizza, Mariagrazia; Rappuoli, Rino

doi:10.1002/1873-3468.13793

Cited by 17 publications

(20 citation statements)

References 85 publications

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“…Because FHbp from two variants are represented in this vaccine, MenB-FHbp offers broad coverage against multiple N. meningitidis FHbp variants ( 246 ). In contrast, 4CMenB is a multi-component vaccine where one of the components is a FHbp that represents only one variant (subfamily B) [reviewed in ( 247 )].…”

Section: Therapeutic and Preventive Strategies Targeting The Pathogenmentioning

confidence: 99%

Hijacking Factor H for Complement Immune Evasion

et al. 2021

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The complement system is an essential player in innate and adaptive immunity. It consists of three pathways (alternative, classical, and lectin) that initiate either spontaneously (alternative) or in response to danger (all pathways). Complement leads to numerous outcomes detrimental to invaders, including direct killing by formation of the pore-forming membrane attack complex, recruitment of immune cells to sites of invasion, facilitation of phagocytosis, and enhancement of cellular immune responses. Pathogens must overcome the complement system to survive in the host. A common strategy used by pathogens to evade complement is hijacking host complement regulators. Complement regulators prevent attack of host cells and include a collection of membrane-bound and fluid phase proteins. Factor H (FH), a fluid phase complement regulatory protein, controls the alternative pathway (AP) both in the fluid phase of the human body and on cell surfaces. In order to prevent complement activation and amplification on host cells and tissues, FH recognizes host cell-specific polyanionic markers in combination with complement C3 fragments. FH suppresses AP complement-mediated attack by accelerating decay of convertases and by helping to inactivate C3 fragments on host cells. Pathogens, most of which do not have polyanionic markers, are not recognized by FH. Numerous pathogens, including certain bacteria, viruses, protozoa, helminths, and fungi, can recruit FH to protect themselves against host-mediated complement attack, using either specific receptors and/or molecular mimicry to appear more like a host cell. This review will explore pathogen complement evasion mechanisms involving FH recruitment with an emphasis on: (a) characterizing the structural properties and expression patterns of pathogen FH binding proteins, as well as other strategies used by pathogens to capture FH; (b) classifying domains of FH important in pathogen interaction; and (c) discussing existing and potential treatment strategies that target FH interactions with pathogens. Overall, many pathogens use FH to avoid complement attack and appreciating the commonalities across these diverse microorganisms deepens the understanding of complement in microbiology.

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Section: Therapeutic and Preventive Strategies Targeting The Pathogenmentioning

confidence: 99%

Hijacking Factor H for Complement Immune Evasion

et al. 2021

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“…are in fact at a higher risk of developing meningococcal infection (Haralambous et al, 2006). fHbp is also considered an interesting candidate for vaccine development (Principato, Pizza, & Rappuoli, 2020).…”

Section: A Play Of Deception and Evasion: Carbohydrate-targeted Complement Escape By Microbes And Parasitesmentioning

confidence: 99%

“…Due to fHbp expression at the pathogen surface, individuals with elevated levels of FH (typically due to a mutation in the promoter region) are in fact at a higher risk of developing meningococcal infection (Haralambous et al, 2006). fHbp is also considered an interesting candidate for vaccine development (Principato, Pizza, & Rappuoli, 2020).…”

Section: A Play Of Deception and Evasion: Carbohydrate‐targeted Complement Escape By Microbes And Parasitesmentioning

confidence: 99%

Sweet turning bitter: Carbohydrate sensing of complement in host defence and disease

Hevey

Pouw

Harris

et al. 2020

British J Pharmacology

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The complement system plays a major role in threat recognition and in orchestrating responses to microbial intruders and accumulating debris. This immune surveillance is largely driven by lectins that sense carbohydrate signatures on foreign, diseased and healthy host cells and act as complement activators, regulators or receptors to shape appropriate immune responses. While carbohydrate sensing protects our bodies, misguided or impaired recognition can contribute to disease. Moreover, pathogenic microbes have evolved to evade complement by mimicking host signatures. While complement is recognized as a disease factor, we only slowly start to appreciate the role of carbohydrate interactions in the underlying processes. A better understanding of complement's sweet side will contribute to a better description of disease mechanisms and enhanced diagnostic and therapeutic options. This review introduces the key components in complement‐mediated carbohydrate sensing, discusses their role in health and disease, and touches on the potential effects of carbohydrate‐related disease intervention. Linked Articles This article is part of a themed issue on Canonical and non‐canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc

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“…In 2008, we wrote an article about considering microbial inhibitors as vaccines [12]. To our great satisfaction, this has now become reality, because two novel vaccines against group B meningococcus based on complement factor H-binding proteins are available on the market [13]. The novel concept was to realize that, for an efficient vaccine-induced immune response, it is important to understand the key virulence mechanisms of the disease-causing pathogen.…”

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confidence: 99%

“…Many pathogens escape complement attack by binding the soluble complement inhibitor factor H, a strategy that also the human body uses to distinguish self from nonself [15]. Thus, it is natural to have microbial factor H-binding proteins (FHBP) in vaccines, as is the case in group B meningococcal vaccines [13]. If vaccines contain proteins that bind too strongly to host factor H, they may be scavenged away from reaching antigen-capturing dendritic cells.…”

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confidence: 99%