Structural Basis for a Convergent Immune Response against Ebola Virus

Cohen-Dvashi, Hadas; Zehner, Matthias; Ehrhardt, Stefanie; Katz, Michael J.; Elad, Nadav; Klein, Florian; Diskin, Ron

doi:10.1016/j.chom.2020.01.007

Cited by 28 publications

(36 citation statements)

References 41 publications

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“…Antibodies that share the same germline gene usage and similar molecular interactions with antigens have been observed in other viral infections, including Ebola, Zika, and influenza, as well as chronic HIV-1 infection. The VH3-15/VL1-40-based class of antibodies targeting the NPC1-receptor-binding site on Ebola GP has been reported as a common response in individuals infected with the Ebola virus or vaccinated with Ebola virus vaccine rVSV-ZEBOV [38,39]. The VH3-23/VK1-5 antibodies specifically recognize the lateral ridge of ZIKV EDIII [40].…”

Section: Discussionmentioning

confidence: 99%

Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients

Yan

Huang

et al. 2021

Emerging Microbes & Infections

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Monoclonal antibodies (mAbs) encoded by targeting the spike receptor-binding domain (RBD) have been isolated from different COVID-19 patients. However, the existence and prevalence of shared VH3-53-encoded antibodies in the antibody repertoires is not clear. Using antibody repertoire sequencing, we found that the usage of VH3-53 increased after SARS-CoV-2 infection. A highly shared VH3-53-J6 clonotype was identified in 9 out of 13 COVID-19 patients. This clonotype was derived from convergent gene rearrangements with few somatic hypermutations and was evolutionary conserved. We synthesized 34 repertoire-deduced novel VH3-53-J6 heavy chains and paired with a common IGKV1-9 light chain to produce recombinant mAbs. Most of these recombinant mAbs (23/34) possess RBD binding and virus-neutralizing activities, and recognize ACE2 binding site via the same molecular interface. Our computational analysis, validated by laboratory experiments, revealed that VH3-53 antibodies targeting RBD are commonly present in COVID-19 patients' antibody repertoires, indicating many people have germline-like precursor sequences to rapidly generate SARS-CoV-2 neutralizing antibodies. Moreover, antigenspecific mAbs can be digitally obtained through antibody repertoire sequencing and computational analysis.

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Section: Discussionmentioning

confidence: 99%

Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients

Yan

Huang

et al. 2021

Emerging Microbes & Infections

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“…The IGHV germline of ERBs contains numerous gene expansions relative to human orthologs (Figure 1). We observed that several of the ERB IGHV genes present, and, in some cases, expanded, were associated with V(D)J rearrangement signatures for specific pathogens (Table S1; Cohen-Dvashi et al, 2020;Watson et al, 2017), suggesting that the ERB may be equipped with an IGHV repertoire prone to generating antibodies that can bind to zoonotic viruses. The expansion of the IGHJ4 genes in ERBs may reflect its important role in V(D)J recombination; however, its impact in B cell diversity and antibody specificity is still unknown (Arnaout et al, 2011).…”

Section: Distinct Features Found On the Igh Locusmentioning

confidence: 94%

Genomic features of humoral immunity support tolerance model in Egyptian rousette bats

et al. 2021

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“…For instance, the VRC01 class of HIV-specific antibodies often have a motif that includes a 5-residue LCDR3 and a short and flexible LCDR1 [39][40][41][42] . Importantly, recent work has identified a public clonotype targeting the Ebola virus glycoprotein (GP) that is elicited after natural infection or vaccination 43,44 . These GP-specific antibodies are encoded by IGHV3-15 and IGLV1-40, make conserved light chain and heavy chain contacts with GP, and have been isolated from multiple individuals.…”

Section: Discussionmentioning

confidence: 99%

Canonical features of human antibodies recognizing the influenza hemagglutinin trimer interface

Zost

Dong

Gilchuk

et al. 2021

Preprint

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SUMMARYBroadly reactive antibodies targeting the influenza A hemagglutinin (HA) head domain are thought to be rare and to require extensive somatic mutations or unusual structural features to achieve breadth against divergent HA subtypes. Here we describe common genetic and structural features of diverse human antibodies from several individuals recognizing the trimer interface (TI) of the influenza HA head, a recently identified site of vulnerability1–3. We examined the sequence of TI-reactive antibodies, determined crystal structures for TI antibody-antigen complexes, and analyzed the contact residues of the antibodies on HA to discover common genetic and structural features of TI antibodies. Our data reveal that many TI antibodies are encoded by a light chain variable gene segment incorporating a shared somatic mutation. In addition, these antibodies have a shared acidic residue in the heavy chain despite originating from diverse heavy chain variable gene segments. These studies show that the TI region of influenza HA is a major antigenic site with conserved structural features that are recognized by a common human B cell public clonotype. The canonical nature of this antibody-antigen interaction suggests that the TI epitope might serve as an important new target for structure-based vaccine design.

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Structural Basis for a Convergent Immune Response against Ebola Virus

Cited by 28 publications

References 41 publications

Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients

Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients

Genomic features of humoral immunity support tolerance model in Egyptian rousette bats

Canonical features of human antibodies recognizing the influenza hemagglutinin trimer interface

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