Neutralizing antibody titers against emerging SARS-CoV-2 strains

Current vaccines were developed targeting initial SARS-CoV-2 that emerged in 2019. Spike protein mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines. Recent emergence of new SARSCoV-2 variants B.1.1.7 in the UK. and B.1.351 in South Africa is of concern.

South African variant B.1.351 is markedly more resistant to neutralization by convalescent plasma (~11-33 fold) and vaccine sera (~6.5-8.6 fold). 

. B.1.351 contains 9 spike mutations in addition to D614G, including a cluster of mutations (e.g., 242-244del & R246I) in NTD, three mutations (K417N, E484K, & N501Y) in RBD, and one mutation (A701V) near the furin cleavage site 

Many of the mutations reside in the antigenic supersite in NTD or in the ACE2-binding site (also known as the receptor binding motif—RBM) that is a major target of potent virus-neutralizing antibodies. 

Vaccinee Sera 

Sera were obtained from 12 participants of a Phase 1 clinical trial of Moderna SARS-Co2 mRNA-1273 Vaccine conducted at the NIH. These volunteers received two immunizations with the vaccine (100 µg) on days 0 and 28, and blood was collected on day 43. 

Additional vaccinee sera were obtained at Columbia University Irving Medical Center from 10 health care workers who got the Pfizer BNT162b2 Covid-19 Vaccine at the clinical dose on days 0 and 21. Blood was collected on day 28 or later. 

Results:

Vaccines

Each vaccinee serum sample was assayed for neutralization against UK∆8 variant, SA∆9 variant, and WT pseudoviruses. 

Only a minority of sera to have lost >2-fold neutralizing activity against UK∆8 variant, whereas every sample lost activity against SA∆9 variant (South Africa), ranging from slight to substantial. 

Monoclonal Antibodies:

LY-CoV555 is inactive against SA∆9, and the activity of REGN10933 is impaired, while its combination with REGN10987 remains potent. Several other mAbs in development are similarly impaired 

N-terminal domain (NTD) 

Conclusion:

Despite the observed decreases, titers in human vaccinee sera against the B.1.351 variant remained at ~1/300. Taken together these data demonstrate reduced but still significant neutralization against the full B.1.351 variant following mRNA-1273 vaccination. Eventually vaccines and monoclonal antibodies will need to be updated to deal with the decreasing efficacy of current therapies.

Reference:

1. Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization

Pengfei Wang, Liu Lihong, Sho Iketani, Yang Luo, Yicheng Guo, Maple Wang, Jian Yu, Baoshan Zhang, Peter D Kwong, Barney S Graham, John R Mascola, Jennifer Y Chang, Michael T Yin, Magdalena E Sobieszczyk, Christos A Kyratsous, Lawrence Shapiro, Zizhang Sheng, Manoj S Nair, Yaoxing Huang, David D Ho

bioRxiv 2021.01.25.428137; doi: https://doi.org/10.1101/2021.01.25.428137

2. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants

Kai Wu, Anne P. Werner, Juan I. Moliva, Matthew Koch, Angela Choi, Guillaume B. E. Stewart-Jones, Hamilton Bennett, Seyhan Boyoglu-Barnum, Wei Shi, Barney S. Graham, Andrea Carfi, Kizzmekia S. Corbett, Robert A. Seder, Darin K. Edwards

bioRxiv 2021.01.25.427948; doi: https://doi.org/10.1101/2021.01.25.427948