Successful post-exposure prophylaxis of Ebola infected non-human primates using Ebola glycoprotein-specific equine IgG

Pyankov, Oleg V.; Setoh, Yin Xiang; Боднев, С. А.; Edmonds, Judith H.; Pyankova, Olga G.; Pyankov, Stepan A.; Pali, Gabor; Belford, Shane; Lu, Lu; La, Mylinh; Lovrecz, George O.; Volchkova, Valentina A.; Chappell, Keith J.; Watterson, Daniel; Marsh, Glenn A.; Young, Paul R.; Agafonov, A. P.; Farmer, Jillann F; Volchkov, Victor E.; Suhrbier, Andreas; Khromykh, Alexander A.

doi:10.1038/srep41537

Cited by 15 publications

(13 citation statements)

References 44 publications

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“…Besides emerging and re-emerging infectious diseases, heterologous polyclonal antibody therapies are also useful to treat longstanding neglected tropical diseases 18 . Equine antivenom products are routinely produced in both high-and low-income countries 16 and indicate a high immunogenicity of the trimeric S protein used herein.…”

Section: Discussionmentioning

confidence: 99%

Potent neutralizing equine antibodies raised against recombinant SARS-CoV-2 spike protein for COVID-19 passive immunization therapy

Cunha

Stolet

Strauch

et al. 2020

Preprint

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COVID-19 pandemic caused approximately 750,000 deaths and over 20 million confirmed cases of infection by SARS-CoV-2 within 8 months since the emergence of the virus. While there are no vaccines approved and considering the difficulty in meeting the large vaccination demand worldwide, the potential use of passive immunization should be considered based on existing successful therapies against many diseases. Here we demonstrate that hyperimmune globulin preparations raised in horses against the recombinant trimeric spike (S) glycoprotein of SARS-CoV-2 in the prefusion conformation provide very high ELISA titers as well as highly potent neutralizing activity against SARS-CoV-2. Five horses were subcutaneously inoculated for 6 weeks with the recombinant S protein (ectodomain, residues 1-1208). Four out of the 5 horses presented a strong immune response. Considering the average of all 5 horses, ELISA titers above 1:1,000,000 and neutralizing titers (PRNT90) reaching 1:14,604 were observed. When compared with the plasma of three convalescent COVID-19 patients, sera of immunized horses displayed approximately 140-fold higher neutralizing titers measured as PRNT90. To prevent eventual side effects caused by horse antiserum, IgG was digested with pepsin and purified by fractional salt precipitation to eliminate Fc fragments, a process that is industrially used for the production of passive immunization F(ab')2 concentrates against rabies, tetanus and snake venoms. The high neutralizing titers against SARS-CoV-2 obtained for the unprocessed sera were confirmed for the F(ab')2 fragments and were 150-fold higher than the PRNT90 neutralizing titers of plasma of three COVID-19 convalescent patients. The great advantage of using the recombinant trimeric S glycoprotein is that it is safe and provides quick adaptive immunity in horses. Our data show the perspective of using hyperimmune anti-SARS-CoV-2 F(ab')2 preparations as a passive immunization therapy in humans, similar to therapies that have been safely used for decades against rabies, tetanus and snake venoms.

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Section: Discussionmentioning

confidence: 99%

Potent neutralizing equine antibodies raised against recombinant SARS-CoV-2 spike protein for COVID-19 passive immunization therapy

Cunha

Stolet

Strauch

et al. 2020

Preprint

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“…Human convalescent plasma has not met with the desired results 8 . Puri ed immunoglobulins obtained from hyper-immune equine sera has been an effective and time-tested approach in various infections such as diphtheria, tetanus, rabies and bites from snakes, scorpions, arachnids and more recently SARS-CoV-1, MERS-CoV, Ebola and avian in uenza virus 23,24,25,26 .…”

Section: Discussionmentioning

confidence: 99%

Development of equine antisera with high neutralizing activity against SARS-CoV-2

Sapkal

Yadav

Deshpande

et al. 2020

Preprint

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The pandemic of COVID -19 caused by SARS-CoV-2 is leading to a humongous impact on the mankind with over a million people succumbing to it worldwide. Although there are few drugs approved for the treatment, there is not yet a safe and effective vaccine available for COVID-19. Also, the passive immunization therapy with convalescent plasma, though potentially an effective treatment option for other viral disease has limitation of availability. The prior use of immunoglobulins generated in animals has proven to be effective in several viral and bacterial diseases. Here, we report the development and evaluation of equine hyper immune globulin raised against inactivated SARS-CoV-2 virus. Post immunization neutralization titres of the equines demonstrated high neutralizing antibodies. To minimize the adverse effects, the immunoglobulins were digested with pepsin, and purified to obtain the F(ab’)2 fragments. The average nAb titre of the purified bulk was 22,927 and correlated with high IgG binding efficiency in ELISA. The quality control assessments of the different batches proved to have consistent nAb titres. The study provides evidence of the potential of generating highly purified F(ab’)2 from equines against SARS-CoV-2 that can demonstrate consistent and high neutralization activity. Further, in-vivo testing for efficacy of this indigenously developed, cost effective product will pave the way to clinical evaluation.

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“…Multiple failures of the early attempts to treat filovirus infections by passively-transferred antibodies might be explained by insufficiently high doses of antibodies administered (reviewed in Kuhn, 2008). In contrast, the more recent successful experimental antibody treatments of filovirus infections used extremely high concentrations of monoclonal (Corti et al, 2016; Qiu et al, 2012; Qiu et al, 2014) or polyclonal (Dye et al, 2012; Kudoyarova-Zubavichene et al, 1999; Pyankov et al, 2017) antibodies, which are likely to overcome the ADE effect. In this context, introduction of mutations in Fc domains that disable the interaction with Fcγ receptors may be desirable.…”

Section: Discussionmentioning

confidence: 99%

Antibody-Dependent Enhancement of Ebola Virus Infection by Human Antibodies Isolated from Survivors

et al. 2018

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Some monoclonal antibodies (mAbs) recovered from survivors of filovirus infections can protect against infection. It is currently unknown whether natural infection also induces some antibodies with the capacity for antibody-dependent enhancement (ADE). A panel of mAbs obtained from human survivors of filovirus infection caused by Ebola, Bundibugyo, or Marburg viruses was evaluated for their ability to facilitate ADE. ADE was observed readily with all mAbs examined at sub-neutralizing concentrations, and this effect was not restricted to mAbs with a particular epitope specificity, neutralizing capacity, or subclass. Blocking of specific Fcγ receptors reduced but did not abolish ADE that was associated with high-affinity binding antibodies, suggesting that lower-affinity interactions still cause ADE. Mutations of Fc fragments of an mAb that altered its interaction with Fc receptors rendered the antibody partially protective in vivo at a low dose, suggesting that ADE counteracts antibody-mediated protection and facilitates dissemination of filovirus infections.

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Successful post-exposure prophylaxis of Ebola infected non-human primates using Ebola glycoprotein-specific equine IgG

Cited by 15 publications

References 44 publications

Potent neutralizing equine antibodies raised against recombinant SARS-CoV-2 spike protein for COVID-19 passive immunization therapy

Potent neutralizing equine antibodies raised against recombinant SARS-CoV-2 spike protein for COVID-19 passive immunization therapy

Development of equine antisera with high neutralizing activity against SARS-CoV-2

Antibody-Dependent Enhancement of Ebola Virus Infection by Human Antibodies Isolated from Survivors

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