Researchers in the UK and South Africa have identified alpaca-derived nanobodies that neutralize variants of the novel SARS-CoV-2. One particular VOC is B.1.351 lineage identified in South Africa. These amino acid changes in the spike, together with the high prevalence of B.1.351 in the South African population, suggest that this variant may be able to evade the neutralizing antibody response that is triggered by natural infection and vaccination. The evolution of neutralization escape mutations poses significant challenges to vaccine design and the global management of COVID-19 since no highly effective treatments for the disease are yet available.
Nanobodies that have previously been raised against a range of infectious viruses, including HIV, hepatitis B, influenza, rabies, and polio have exhibited potent neutralizing activity. Nanobodies exhibit high thermal and chemical stability and a high affinity for their target antigens. They are also able to access epitopes that are inaccessible to conventional antibodies. The team set out to investigate recombinant alpaca antibodies as novel therapeutics to neutralize SARS-CoV-2 variants such as B.1.351.An alpaca was immunized with recombinant subunit 1 of the SARS-CoV-2 spike protein and the animal’s serum was tested 2, 4, and 8 weeks later for neutralizing activity against the SARS-CoV-2 variant CVR-GLA-1.
Eight different nanobody sequences that bound to the recombinant S1 protein were isolated, namely A1, A2, B1, B7, C3, C9, C12, and H4. When the eight nanobodies were tested against the CVR-GLA-1 variant, four (A1, A2, C3 & C9) displayed potent neutralizing activity. Three of the nanobodies – A1, C3, and C9 – also potently neutralized the B.1.1 variant, but nanobodies C3 and C9 showed no neutralization activity against B.1.351. However, nanobody A1 displayed potent neutralizing activity against both B.1.1 and the B.1.351 variant. A1 nanobody may target an epitope that is conserved between variants. This epitope may not be under selective pressure in the general population.
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