Abstract
Emergence of variants of concern (VOC) during the COVID-19 pandemic has contributed to the decreased efficacy of therapeutic monoclonal antibody treatments for severe cases of SARS-CoV-2 infection. In addition, the cost of creating these therapeutic treatments is high, making their implementation in low- to middle-income countries devastated by the pandemic very difficult. Here, we explored the use of polyclonal EpF(ab’) 2 antibodies generated through the immunization of horses with SARS-CoV-2 WA-1 RBD conjugated to HBsAg nanoparticles as a low-cost therapeutic treatment for severe cases of disease. We determined that the equine EpF(ab’) 2 bind RBD and neutralize ACE2 receptor binding by virus for all VOC strains tested except Omicron. Despite its relatively quick clearance from peripheral circulation, a 100μg dose of EpF(ab’) 2 was able to fully protect mice against severe disease phenotypes following intranasal SARS-CoV-2 challenge with Alpha and Beta variants. EpF(ab’) 2 administration increased survival while subsequently lowering disease scores and viral RNA burden in disease-relevant tissues. No significant improvement in survival outcomes or disease scores was observed in EpF(ab’) 2 -treated mice challenged using the Delta variant at 10μg or 100µg doses. Overall, the data presented here provide a proof of concept for the use of EpF(ab’) 2 in the prevention of severe SARS-CoV-2 infections and underscore the need for either variant-specific treatments or variant-independent therapeutics for COVID-19.
Keywords: COVID-19; EpF(ab’)2; Equine F(ab’)2; K18-hACE2 transgenic mice; SARS-CoV-2; passive immunization; polyclonal antibodies; variant of concern (VOC).
【저자키워드】 COVID-19, passive immunization, SARS-CoV-2, polyclonal antibodies, Variant of concern (VOC)., K18-hACE2 transgenic mice, Equine F(ab’)2, EpF(ab’)2, 【초록키워드】 Treatment, Efficacy, pandemic, antibody, VoC, SARS-COV-2 infection, COVID-19 pandemic, variant, Infection, variants of concern, outcome, omicron, delta variant, virus, immunization, variants, survival, mice, RBD, emergence, implementation, therapeutic, phenotype, Beta, Viral RNA, disease, intranasal, monoclonal antibody treatment, K18-hACE2, administration, dose, strain, severe disease, peripheral circulation, tissues, increased survival, HBsAg, Severe case, doses, equine, clearance, Therapeutic treatment, transgenic, country, polyclonal, severe SARS-CoV-2, neutralize, PROTECT, ACE2 receptor binding, tested, addition, contributed, creating, 【제목키워드】 Beta, Fab, equine, variants of SARS-CoV-2, PROTECT,