Title : Equine polyclonal F(ab)’2 as a rapid and strong therapeutic answer against potential new SARS-CoV-2 surge
Abstract:
Successive sub-lineages of Omicron have spread since the occurrence of BA.1 in November 2021. Identified in July 2022, BQ.1 and BQ.1.1 expanded dramatically in Europe and North America. XBB and XBB.1 were first identified in India in mid-August 2022 and quickly spread to become predominant worldwide. The XBB lineage originated from a recombination of two BA.2-derived variants (BJ.1 and BM.1.1.1) and progressively replaced most of previous Omicron strains. Members of this lineage are characterized by enhanced transmissibility rates and immune evasion properties. The rapid rise of these subvariants and their extensive array of spike mutations raised concerns that they will further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody (mAb) based therapeutics. This was confirmed by many publications showing that human convalescent plasma from patient having received 3 shots of Wuhan-based vaccines were not able to efficiently seroneutralize XBB.1, XBB, BQ.1.1 and BQ.1 variants. Confirming this continuous drift in SARS-CoV-2 mutants, the BA.2.86 lineage first detected in August 2023 has rapidly evolved and led to the emergence of the JN.1 sublineage in September 2023. As of December 2023, JN.1 was sharply increasing in frequency in Europe and USA.
Both BQ and XBB sublineages are now completely resistant to bebtelovimab, leaving us with no authorized antibody for treatment use.
Leveraging its equine polyclonal F(ab')2 platform, Fabentech has developed FBR-002 product, purified from Immunoglobulins obtained after horse immunization with SARS-Co2 Wuhan spike protein. FBR-002 represents a pertinent therapy candidate for treating patients hospitalized with COVID-19 because of its polyclonality, which enables the targeting of multiple epitopes of the spike protein, limiting the risk of viral escape if new strains emerge.
Although FBR-002 showed a decreased activity level for the seroneutralization of D614G mutant-related strains compared to the last variants, the Fab’entech developed polyclonal F’(ab)’2 was still able to neutralize BQ.1.1, XBB.1.5 and XBB.1.16 strains with strong potency. In comparison, Sotrovimab seroneutralisation was barely detectable.
Fab’entech is currently evaluating the seroneutralisation activity of FBR-002 against the latest variant JN.1 derived from BA.2.86.1 in comparison to the activity of various human convalescent plasmas.
In a context of rapid evolution and adaptation of emerging Covid-19 variants, and a lack of activity of mAbs, the polyclonal antibody approach should be considered as a particularly relevant therapeutic product for the treatment of high-risk populations such as immunocompromised patients.
