A group from Joint Research Center for Human Retrovirus infection, Kumamoto University, Japan, etc. has reported that mAbs induced in convalescent patients with COVID-19 and with high affinity for the SARS-CoV-2 RBD efficiently cross-neutralize B.1.351 and P.1.
https://pubmed.ncbi.nlm.nih.gov/34237284/
1102 kinds of IgGs were obtained from two COVID-19 covalescent patients who were infected with SARS-CoV-2 in March, 2020. Among these, 88 kinds bound SARS-CoV-2 Spike, and its 10% bound RBD, and further, IgGs showing neutralizing activity were 5 kinds.
Obtained 5 IgGs: one IgG targeting NTD = 6-74, four IgGs targeting RBD = 3-5, 8-92, 9-105, 10-121.
The neutralization potency of mAbs was examined against pseudoviruses expressing S proteins from the emerging SARS-CoV-2 variants, B.1.1.7, B.1.351, P.1, and mink cluster 5 . Most mAbs neutralized B.1.1.7 and mink cluster 5 variants at the same level as the prototypic 614G pseudovirus. B.1.1.7 was slightly resistant to mAbs 6-74 (3.3-fold) and 3-5 (6.0-fold). The NTD-targeting mAb 6-74 was not effective against mink cluster 5. Neutralization resistance was observed for P.1 and especially B1.351. P.1 was not neutralized by mAbs 6-74 and 3-5 and required a high concentration of the other mAbs (2.6- to 8.0-fold). B.1.351 was neutralized by mAbs 9-105 and 10-121, but not by mAbs 6-74, 3-5, and 8-92. The potencies of 9-105 and 10-121 were reduced against B.1.351 (6.0- and 19-fold, respectively).
All of the variants tested showed resistance to 6-74, suggesting that variants can easily escape from this mAb targeting the NTD, perhaps due to mutations in the NTD. The efficacy of the RBD-targeting mAbs was decreased against P.1 and B.1.351, suggesting that the K417N/T, E484K, and N501Y mutations in the RBD region are critical for the resistance of these variants. Analysis of single mutants revealed that K417N and K417T were critical for escape from 3-5 and slightly decreased the potency of 8-92. E484K and N501Y single mutation did not confer resistance to these RBD-targeting mAbs. However, pseudoviruses with triple RBD mutations, especially the combination of K417N, E484K, and N501Y, were resistant to 3-5, 8-92, and 10-121. Interestingly, the potency of 9-105 was affected by K417N single mutation but neutralized triple mutants at the same level as prototype pseudovirus. It is important to monitor the emergence of new variants and identify the mutations associated with immune escape.