Intranasal administration of a monoclonal neutralizing antibody protects mice against SARS-CoV-2 infection

Halwe, Sandro; Kupke, Alexandra; Vanshylla, Kanika; Liberta, Falk; Gruell, Henning; Zehner, Matthias; Rohde, Cornelius; Kraehling, Verena; Gellhorn-Serra, Michelle; Kreer, Christoph; Kluever, Michael; Sauerhering, Lucie; Schmidt, J; Cai, Zengyu; Han, Fei; Young, David; Yang, Guangwei; Widera, Marek; Koch, Manuel; Werner, Anke; Kaemper, Lennart; Becker, Nico; Marlow, Michael S.; Eickmann, Markus; Ciesek, Sandra; Schiele, Felix; Klein, Florian; Becker, Stephan

doi:10.1101/2021.06.09.447662

Cited by 12 publications

(3 citation statements)

References 72 publications

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“…Romlusevimab ( 28 ), bebtelovimab ( 29 ), and ensovibep (DARPin) ( 30 ) retained potency comparable to D614G, albeit with varying degrees of absolute potency. DZIF-10c ( 31 ), tixagevimab ( 32 ), and ADG20 ( 33 ) retained partial potency to varying degrees. The remaining neutralizing antibodies [amubarvimab ( 28 ), cilgavimab ( 32 ), bamlanivimab ( 34 ), etesevimab ( 34 ), ADG10 ( 33 ), and C-144 ( 35 )] were completely resistant at the highest concentrations tested.…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 BA.1 variant is neutralized by vaccine booster–elicited serum but evades most convalescent serum and therapeutic antibodies

et al. 2022

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The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms about the effectiveness of current medical countermeasures. To address this concern, we measured neutralization of the Omicron BA.1 variant pseudovirus by post-vaccination serum samples after two and three immunizations with the Pfizer/BioNTech162b2 SARS-CoV-2 mRNA (Pfizer/BNT162b2) vaccine, convalescent serum samples from unvaccinated individuals infected by different variants, and clinical-stage therapeutic antibodies. We found that titers against the Omicron variant were low or undetectable after two immunizations and in many convalescent serum samples, regardless of the infecting variant. A booster vaccination increased titers more than 30-fold against Omicron to values comparable to those seen against the D614G variant after two immunizations. Neither age nor sex were associated with differences in post-vaccination antibody responses. We also evaluated eighteen clinical-stage therapeutic antibody products and an antibody mimetic protein product obtained directly from the manufacturers. Five monoclonal antibodies, the antibody mimetic protein, three antibody cocktails, and two polyclonal antibody preparations retained measurable neutralization activity against Omicron with a varying degree of potency. Of these, only three retained potencies comparable to the D614G variant. Two therapeutic antibody cocktails in the tested panel that are authorized for emergency use in the United States did not neutralize Omicron. These findings underscore the potential benefit of mRNA vaccine boosters for protection against Omicron and the need for rapid development of antibody therapeutics that maintain potency against emerging variants.

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Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 BA.1 variant is neutralized by vaccine booster–elicited serum but evades most convalescent serum and therapeutic antibodies

et al. 2022

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“…To detect viral RNA in the lungs, fixed paraffin-embedded tissue sections were mounted on glass slides and analyzed by in situ hybridization as described previously (Halwe et al, 2021;Tscherne et al, 2021). For this, the RNAscopeâ 2.5 HD Assay -RED Kit (Bio-Techne, cat.…”

Section: In Situ Hybridisationmentioning

confidence: 99%

Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after TH2-biased immunization

et al. 2022

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“…The neutralizing activity of mouse serum antibodies was investigated based on a previously published protocol (47). Briefly, samples were serially diluted in 96-well plates starting from a 1:16 serum dilution.…”

Section: Sars-cov-2 Virus Neutralization Test (Vnt100)mentioning

confidence: 99%

Stabilized recombinant SARS-CoV-2 spike antigen enhances vaccine immunogenicity and protective capacity

Natrup¹,

Tscherne²,

Dahlke³

et al. 2022

Journal of Clinical Investigation

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The SARS-CoV-2 spike (S) glycoprotein is synthesized as large precursor protein and must be activated by proteolytic cleavage into S1 and S2. A recombinant modified vaccinia virus Ankara (MVA) expressing native, full-length S protein (MVA-SARS-2-S) is currently under investigation as candidate vaccine in phase I clinical studies. Initial results from immunogenicity monitoring revealed induction of S-specific antibodies binding to S2, but low-level antibody responses to the S1 domain. Follow-up investigations of native S antigen synthesis in MVA-SARS-2-S infected cells revealed limited levels of S1 protein on the cell surface. In contrast, we found superior S1 cell surface presentation upon infection with a recombinant MVA expressing a stabilized version of SARS-CoV-2 S protein with an inactivated S1/2 cleavage site and K986→P and V987→P mutations (MVA-SARS-2-ST). When comparing immunogenicity of MVA vector vaccines, mice vaccinated with MVA-SARS-2-ST mounted substantial levels of S broadly reactive antibodies that effectively neutralized different SARS-CoV-2 variants. Importantly, intramuscular MVA-SARS-2-ST immunization of hamsters and mice resulted in potent immune responses upon challenge infection and protected from disease and severe lung pathology. Our results suggest that MVA-SARS-2-ST represents an improved clinical candidate vaccine and that the presence of plasma membrane-bound S1 is highly beneficial to induce protective antibody levels.

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Intranasal administration of a monoclonal neutralizing antibody protects mice against SARS-CoV-2 infection

Cited by 12 publications

References 72 publications

SARS-CoV-2 BA.1 variant is neutralized by vaccine booster–elicited serum but evades most convalescent serum and therapeutic antibodies

SARS-CoV-2 BA.1 variant is neutralized by vaccine booster–elicited serum but evades most convalescent serum and therapeutic antibodies

Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after TH2-biased immunization

Stabilized recombinant SARS-CoV-2 spike antigen enhances vaccine immunogenicity and protective capacity

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