Increased in vitro neutralizing activity of SARS-CoV-2 IgA1 dimers compared to monomers and IgG

Sun, Lin; Kallolimath, Somanath; Palt, Roman; Stiasny, Karin; Mayrhofer, Patrick; Maresch, Daniel; Eidenberger, Lukas; Steinkellner, Herta

doi:10.1073/pnas.2107148118

Cited by 46 publications

(56 citation statements)

References 13 publications

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“…In summary, this study demonstrates the optimal combination of CHO-K1 host cell line, expression vector, and fed-batch or continuous bioprocesses to produce the complex spike protein in large amounts at the highest quality and is already used successfully in ongoing serological studies or to develop novel anti-SARS-CoV-2 antibody formats (Garner-Spitzer et al, 2021;Kallolimath et al, 2021;Sun et al, 2021). The availability of viral proteins in high quality and sufficient amounts now allows investigating the biological and virologic basics of SARS-CoV-2 to understand the infection and propagation mechanisms, the virus distribution in the body, the docking of the virus, viral immune evasion, and the immune response mechanism of the human body in more detail.…”

Section: Discussionmentioning

confidence: 94%

Functional Trimeric SARS-CoV-2 Envelope Protein Expressed in Stable CHO Cells

Mayrhofer

Hunjadi

Kunert

2021

Front. Bioeng. Biotechnol.

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a β-coronavirus, is the causative agent of the COVID-19 pandemic. One of the three membrane-bound envelope proteins is the spike protein (S), the one responsible for docking to the cellular surface protein ACE2 enabling infection with SARS-CoV-2. Although the structure of the S-protein has distinct similarities to other viral envelope proteins, robust and straightforward protocols for recombinant expression and purification are not described in the literature. Therefore, most studies are done with truncated versions of the protein, like the receptor-binding domain. To learn more about the interaction of the virus with the ACE2 and other cell surface proteins, it is mandatory to provide recombinant spike protein in high structural quality and adequate quantity. Additional mutant variants will give new insights on virus assembly, infection mechanism, and therapeutic drug development. Here, we describe the development of a recombinant CHO cell line stably expressing the extracellular domain of a trimeric variant of the SARS CoV-2 spike protein and discuss significant parameters to be considered during the expression and purification process.

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Section: Discussionmentioning

confidence: 94%

Functional Trimeric SARS-CoV-2 Envelope Protein Expressed in Stable CHO Cells

Mayrhofer

Hunjadi

Kunert

2021

Front. Bioeng. Biotechnol.

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“…Hence, one can assume that such antibodies if locally present at mucosal surfaces, particularly as dimeric IgAs, could efficiently neutralize and/or eliminate virions and therefore, potentially diminish the risk of infection by SARS-CoV-2 variants. In this regard, longer hinge region and multivalency of IgA1 antibody dimers allow enhancing SARS-CoV-2 neutralization in vitro as compared to their IgG1 counterparts (Sun et al, 2021; Wang et al, 2021b). In line with this, we found that the loss of neutralization activity of Cv2.1169 against BA.1 and BA.2 was greatly rescued by avidity effects of the antibody produced in its dimeric IgA form.…”

Section: Discussionmentioning

confidence: 99%

Potent Human Broadly SARS-CoV-2 Neutralizing IgA and IgG Antibodies Effective Against Omicron BA.1 and BA.2

Planchais

Fernández

Bruel

et al. 2022

Preprint

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Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute to long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide SARS-CoV-2 immunoprofiling in COVID-19 convalescents combining serological, cellular and monoclonal antibody explorations, revealed humoral immunity coordination. Detailed characterization of a hundred SARS-CoV-2 spike memory B-cell monoclonal antibodies uncovered diversity in their repertoire and antiviral functions. The latter were influenced by the targeted spike region with strong Fc-dependent effectors to the S2 subunit and potent neutralizers to the receptor binding domain. Amongst those, Cv2.1169 and Cv2.3194 antibodies cross-neutralized SARS-CoV-2 variants of concern including Omicron BA.1 and BA.2. Cv2.1169, isolated from a mucosa-derived IgA memory B cell, demonstrated potency boost as IgA dimers and therapeutic efficacy as IgG antibodies in animal models. Structural data provided mechanistic clues to Cv2.1169 potency and breadth. Thus, potent broadly neutralizing IgA antibodies elicited in mucosal tissues can stem SARS-CoV-2 infection, and Cv2.1169 and Cv2.3194 are prime candidates for COVID-19 prevention and treatment.

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“…The same holds true in another in vitro setting ( Table 3 ). 124 Nevertheless, more studies are urgently required to assess the safety and therapeutic effects of IgA-enriched products in preventing SARS-CoV-2 infection.…”

Section: Therapeutic Iga Antibodies Against Sars-cov-2mentioning

confidence: 99%

Therapeutic antibodies for COVID-19: is a new age of IgM, IgA and bispecific antibodies coming?

Zhang

Sun

2022

mAbs

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Early humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are dominated by IgM and IgA antibodies, which greatly contribute to virus neutralization at mucosal sites. Given the essential roles of IgM and IgA in the control and elimination of SARS-CoV-2 infection, the mucosal immunity could be exploited for therapeutic and prophylactic purposes. However, almost all neutralizing antibodies that are authorized for emergency use and under clinical development are IgG antibodies, and no vaccine has been developed to boost mucosal immunity for SARS-CoV-2 infection. In addition to IgM and IgA, bispecific antibodies (bsAbs) combine specificities of two antibodies in one molecule, representing an important alternative to monoclonal antibody cocktails. Here, we summarize the latest advances in studies on IgM, IgA and bsAbs against SARS-CoV-2. The current challenges and future directions in vaccine design and antibody-based therapeutics are also discussed.

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Increased in vitro neutralizing activity of SARS-CoV-2 IgA1 dimers compared to monomers and IgG

Cited by 46 publications

References 13 publications

Functional Trimeric SARS-CoV-2 Envelope Protein Expressed in Stable CHO Cells

Functional Trimeric SARS-CoV-2 Envelope Protein Expressed in Stable CHO Cells

Potent Human Broadly SARS-CoV-2 Neutralizing IgA and IgG Antibodies Effective Against Omicron BA.1 and BA.2

Therapeutic antibodies for COVID-19: is a new age of IgM, IgA and bispecific antibodies coming?

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