Human Antibodies Targeting Influenza B Virus Neuraminidase Active Site Are Broadly Protective

Madsen, Anders; Dai, Ya-Nan; McMahon, Meagan; Schmitz, Aaron J.; Turner, Jackson S.; Tan, Jessica; Lei, Tingting; Alsoussi, Wafaa B.; Strohmeier, Shirin; Amor, Mostafa; Mohammed, Bassem M.; Mudd, Philip A.; Simon, Viviana; Fremont, Daved H.; Krammer, Florian; Ellebedy, Ali H.

doi:10.1016/j.immuni.2020.08.015

Cited by 55 publications

(50 citation statements)

References 62 publications

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“…5 B). Research on the human immunodeficiency virus (HIV) and influenza B virus has shown that neutralizing antibodies with more amino acids to form a longer CDR-H3 loops have a better chance of breaking through the blockade of viral-antigen glycosylation to recognize viruses [ 26 , 27 ]. Hence, we compared the amino-acid number of V–J-dominant combinations from the CP group and RTP group.…”

Section: Resultsmentioning

confidence: 99%

Profiling of the immune repertoire in COVID-19 patients with mild, severe, convalescent, or retesting-positive status

Zhou

Zhang

Wang

et al. 2021

Journal of Autoimmunity

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Section: Resultsmentioning

confidence: 99%

Profiling of the immune repertoire in COVID-19 patients with mild, severe, convalescent, or retesting-positive status

Zhou

Zhang

Wang

et al. 2021

Journal of Autoimmunity

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“…Probing of the WSEIV HA and NA was carried out using a panel of broadly cross-reactive human and mouse monoclonal antibodies (mAbs) previously characterized to bind to both antigenic divergent and ancestral lineages of influenza B viruses. 14,[33][34][35][36] Control enzyme linked immunosorbent assays (ELISAs) were performed for these mAbs against the influenza B/Malaysia/2506/2004 virus HA and NA and robust binding profiles for most of the tested antibodies were observed. Five antibodies showed strong binding to the WSEIV HA, namely, 1B5, 4C10, 8G3, 9B9, and 11C12 (all murine mAbs, Fig.…”

Section: Resultsmentioning

confidence: 99%

Functionality of the putative surface glycoproteins of the Wuhan spiny eel influenza virus

Arunkumar

Strohmeier

et al. 2021

Preprint

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A panel of novel influenza-like virus sequences were recently documented in jawless fish, ray-finned fish, and amphibians. Of these, the Wuhan spiny eel influenza virus (WSEIV) was found to phylogenetically cluster with influenza B viruses as a sister clade. Influenza B viruses have been historically documented to circulate only in humans, with certain virus isolates found in harbor seals. It is therefore interesting that a similar virus was potentially found in fish. Here we characterized the functionality and antigenicity of the putative hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins of the WSEIV to better understand this virus and its pandemic potential. Upon functional characterization of NA, we identified that the WSEIV NA-like protein has sialidase activity comparable to B/Malaysia/2506/2004 influenza B virus NA, making it a bona fide neuraminidase that could be inhibited by NA inhibitors. Testing of the functionality of HA was carried out including receptor specificity, stability, and preferential airway protease cleavage and showed very specific binding to monosialic ganglioside 2 (GM2). To probe the degree of conservation of target epitopes, binding of known broadly cross-reactive monoclonal antibodies targeting the influenza B HA and NA, respectively, were assessed through enzyme linked immunosorbent assays against recombinant WSEIV glycoproteins. Human serum samples of patients with antibodies to influenza B viruses were used to determine the cross-reactivity against these novel glycoproteins. Very few monoclonal antibodies - notably including pan NA antibody 1G01 - showed cross-reactivity and reactivity from human sera was basically absent. In summary, we have conducted a functional and antigenic characterization of the glycoproteins of the novel WSEIV to assess if it is indeed a bona fide influenza virus potentially circulating in ray-finned fish.

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“…Neuraminidase (NA) is the second most abundant surface glycoprotein and enables viral egress by catalyzing the cleavage of sialyl oligosaccharide from host cell surfaces [ 130 , 131 ] and can aid in early infection in the airway epithelium by removing virus from natural defense proteins such as mucins [ 132 ]. Although HA has historically been the primary measure of seasonal vaccine efficacy as well as the focus of more recent universal vaccine approaches, there is increasing evidence that humoral immunity against conserved targets on NA confers broad protection in animal studies [ 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. Such targeting is also underscored by lower rates of antigenic drift and shift, compared to HA [ 133 , 134 , 135 , 136 ], providing an approachable target for universal vaccine development.…”

Section: Alternative Universal Vaccine Targetsmentioning

confidence: 99%

“…The development of universal vaccines has been further guided by the discovery and ever-growing list of influenza broadly neutralizing and broadly protective antibodies (bnAbs) that target conserved sites of viral vulnerability, particularly those that interfere with HA function [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. Broad-spectrum antibodies also engage conserved targets on other viral surface proteins, including neuraminidase and M2 [ 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. In this review, we outline and discuss the immunological basis and feasibility of rationally engineering humoral immunity that is refocused upon such target epitopes.…”

Section: Introduction—the Need For Universal Influenza Vaccinesmentioning

confidence: 99%

Antibody Focusing to Conserved Sites of Vulnerability: The Immunological Pathways for ‘Universal’ Influenza Vaccines

Sangesland

Lingwood

2021

Vaccines

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Influenza virus remains a serious public health burden due to ongoing viral evolution. Vaccination remains the best measure of prophylaxis, yet current seasonal vaccines elicit strain-specific neutralizing responses that favor the hypervariable epitopes on the virus. This necessitates yearly reformulations of seasonal vaccines, which can be limited in efficacy and also shortchange pandemic preparedness. Universal vaccine development aims to overcome these deficits by redirecting antibody responses to functionally conserved sites of viral vulnerability to enable broad coverage. However, this is challenging as such antibodies are largely immunologically silent, both following vaccination and infection. Defining and then overcoming the immunological basis for such subdominant or ‘immuno-recessive’ antibody targeting has thus become an important aspect of universal vaccine development. This, coupled with structure-guided immunogen design, has led to proof-of-concept that it is possible to rationally refocus humoral immunity upon normally ‘unseen’ broadly neutralizing antibody targets on influenza virus.

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Human Antibodies Targeting Influenza B Virus Neuraminidase Active Site Are Broadly Protective

Cited by 55 publications

References 62 publications

Profiling of the immune repertoire in COVID-19 patients with mild, severe, convalescent, or retesting-positive status

Profiling of the immune repertoire in COVID-19 patients with mild, severe, convalescent, or retesting-positive status

Functionality of the putative surface glycoproteins of the Wuhan spiny eel influenza virus

Antibody Focusing to Conserved Sites of Vulnerability: The Immunological Pathways for ‘Universal’ Influenza Vaccines

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