SARS-CoV-2 BA.4 infection triggers more cross-reactive neutralizing antibodies than BA.1

SARS-CoV-2 variants of concern (VOCs) differentially trigger neutralizing antibodies with variable cross-neutralizing capacity. Here we show that unlike SARS-CoV-2 Omicron BA.1, which triggered neutralizing antibodies with limited cross-reactivity, BA.4/5 infection triggers highly cross-reactive neutralizing antibodies. Cross-reactivity was observed both in the absence of prior vaccination and also in breakthrough infections following vaccination. This suggests that next-generation vaccines incorporating BA.4, which is spreading globally, might result in enhanced neutralization breadth.

[1]  O. Pybus,et al.  Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa , 2022, Nature Medicine.

[2]  Fei Shao,et al.  BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection , 2022, Nature.

[3]  E. Tartour,et al.  Immunogenicity and Safety of Beta-Adjuvanted Recombinant Booster Vaccine , 2022, medRxiv.

[4]  Qian Wang,et al.  SARS-CoV-2 Omicron BA.2.12.1, BA.4, and BA.5 subvariants evolved to extend antibody evasion , 2022, bioRxiv.

[5]  P. Klenerman,et al.  Further antibody escape by Omicron BA.4 and BA.5 from vaccine and BA.1 serum , 2022, bioRxiv.

[6]  S. Richardson,et al.  Shared N417-Dependent Epitope on the SARS-CoV-2 Omicron, Beta, and Delta Plus Variants , 2022, medRxiv.

[7]  S. Madhi,et al.  Emergence and phenotypic characterization of the global SARS-CoV-2 C.1.2 lineage , 2022, Nature Communications.

[8]  J. Mascola,et al.  mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron , 2022, Cell.

[9]  S. Richardson,et al.  SARS-CoV-2 Omicron triggers cross-reactive neutralization and Fc effector functions in previously vaccinated, but not unvaccinated, individuals , 2022, Cell Host & Microbe.

[10]  S. Richardson,et al.  Ad26.COV2.S breakthrough infections induce high titers of neutralizing antibodies against Omicron and other SARS-CoV-2 variants of concern , 2022, Cell Reports Medicine.

[11]  N. Sullivan,et al.  SARS-CoV-2 Beta and Delta variants trigger Fc effector function with increased cross-reactivity , 2022, Cell Reports Medicine.

[12]  A. Walls,et al.  SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses , 2022, Cell.

[13]  L. Bekker,et al.  Effectiveness of BNT162b2 Vaccine against Omicron Variant in South Africa , 2021, The New England journal of medicine.

[14]  T. Ndung’u,et al.  Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization , 2021, Nature.

[15]  M. Kraemer,et al.  Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa , 2021, Nature.

[16]  D. Sheward,et al.  Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models , 2021, Cell Reports Medicine.

[17]  S. Richardson,et al.  Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner , 2021, Cell Host & Microbe.

[18]  L. Morris,et al.  Cross-Reactive Neutralizing Antibody Responses Elicited by SARS-CoV-2 501Y.V2 (B.1.351) , 2021, The New England journal of medicine.

[19]  T. Ndung’u,et al.  Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma , 2021, Nature.

[20]  L. Morris,et al.  SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma , 2021, bioRxiv.

[21]  I. Di Bartolo,et al.  SARS-CoV-2 RECoVERY: a multi-platform open-source bioinformatic pipeline for the automatic construction and analysis of SARS-CoV-2 genomes from NGS sequencing data , 2021, bioRxiv.

[22]  Edward C. Holmes,et al.  A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology , 2020, Nature Microbiology.