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Polyclonal F(ab')₂ fragments of equine antibodies raised against the spike protein neutralize SARS-CoV-2 variants with high potency.

ABSTRACT: We used the recombinant trimeric spike (S) glycoprotein in the prefusion conformation to immunize horses for the production of hyperimmune globulins against SARS-CoV-2. Serum antibody titers measured by ELISA were above 1:10⁶, and the neutralizing antibody titer against authentic virus (WT) was 1:14,604 (average PRNT₉₀). Plasma from immunized animals was pepsin digested to remove the Fc portion and purified, yielding an F(ab')₂ preparation with PRNT₉₀ titers 150-fold higher than the neutralizing titers in human convalescent plasma. Challenge studies were carried out in hamsters and showed the in vivo ability of equine F(ab')₂ to reduce viral load in the pulmonary tissues and significant clinical improvement determined by weight gain. The neutralization curve by F(ab')₂ was similar against the WT and P.2 variants, but displaced to higher concentrations by 0.39 log units against the P.1 (Gamma) variant. These results support the possibility of using equine F(ab')₂ preparation for the clinical treatment of COVID patients.

SUBMITTER: Cunha LER

PROVIDER: S-EPMC8539203 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Polyclonal F(ab')2 fragments of equine antibodies raised against the spike protein neutralize SARS-CoV-2 variants with high potency.

Cunha Luis Eduardo R LER Stolet Adilson A AA Strauch Marcelo A MA Pereira Victor A R VAR Dumard Carlos H CH Gomes Andre M O AMO Monteiro Fábio L FL Higa Luiza M LM Souza Patrícia N C PNC Fonseca Juliana G JG Pontes Francisco E FE Meirelles Leonardo G R LGR Albuquerque José W M JWM Sacramento Carolina Q CQ Fintelman-Rodrigues Natalia N Lima Tulio M TM Alvim Renata G F RGF Marsili Federico F FF Caldeira Marcella Moreira MM Zingali Russolina B RB de Oliveira Guilherme A P GAP Souza Thiago M L TML Silva Alexandre S AS Muller Rodrigo R Rodrigues Daniela Del Rosário Flores DDRF Jesus da Costa Luciana L Alves Arthur Daniel R ADR Pinto Marcelo Alves MA Oliveira Andréa C AC Guedes Herbert L M HLM Tanuri Amilcar A Castilho Leda R LR Silva Jerson L JL

iScience 20211023 11

We used the recombinant trimeric spike (S) glycoprotein in the prefusion conformation to immunize horses for the production of hyperimmune globulins against SARS-CoV-2. Serum antibody titers measured by ELISA were above 1:106, and the neutralizing antibody titer against authentic virus (WT) was 1:14,604 (average PRNT90). Plasma from immunized animals was pepsin digested to remove the Fc portion and purified, yielding an F(ab')2 preparation with PRNT90 ...[more]

PMID: 34723156

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Project description:Backgroundpassive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2.Methodswe conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984).Findingsbetween August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported.InterpretationAlbeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

Dataset Information

Polyclonal F(ab')₂ fragments of equine antibodies raised against the spike protein neutralize SARS-CoV-2 variants with high potency.

Publications

Polyclonal F(ab')<sub>2</sub> fragments of equine antibodies raised against the spike protein neutralize SARS-CoV-2 variants with high potency.

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