New Research Reveals That Long-Lasting B Cells Are Not Able To Recognize Emerging SARS-CoV-2 Variants!
A new study led by biotech company Adimab LLC that is based in New Hampshire-United States along with researchers from the University of Texas-Austin and also from the division of Infectious Disease and International Health, Dartmouth Hitchcock Medical Center-USA have revealed that long-lasting B cells are not able to recognize emerging SARS-CoV-2 variants
. The startling new discovery has huge implications in the current fight against the current evolving COVID-19 pandemic.
In a detailed analysis of B cells and more than 1,000 different monoclonal antibodies from 8 patients with COVID-19, the study team found that, contrary to previous hypotheses, protective B cell responses to the SARS-CoV-2 spike protein remain stable and continue to evolve over a 5-month period, many months after the initial period of active viral replication.
Alarmingly however, a large proportion of the neutralizing antibodies generated from these long-lasting B cells did not efficiently recognize various emerging SARS-CoV-2 variants from Brazil and South Africa.
The study results from an academia-industry collaboration will help inform the design of future COVID-19 vaccines that work to constrain viral evolution and stimulate better neutralizing antibody and B cell responses against emerging SARS-CoV-2 variants.
In the study abstract, the study team commented, “A comprehensive understanding of the kinetics and evolution of the human B cell response to SARS-CoV-2 infection will facilitate the development of next-generation vaccines and therapies. Here, we longitudinally profiled this response in mild and severe COVID-19 patients over a period of five months. Serum neutralizing antibody (nAb) responses waned rapidly but spike (S)-specific IgG+ memory B cells (MBCs) remained stable or increased over time. Analysis of 1,213 monoclonal antibodies (mAbs) isolated from S-specific MBCs revealed a primarily de novo response that displayed increased somatic hypermutation, binding affinity, and neutralization potency over time, providing evidence for prolonged antibody affinity maturation. B cell immunodominance hierarchies were similar across donor repertoires and remained relatively stable as the immune response progressed. Cross-reactive B cell populations, likely re-called from prior endemic beta-coronavirus exposures, comprised a small but stable fraction of the repertoires and did not contribute to the neutralizing response. The neutralizing antibody response was dominated by public clonotypes that displayed significantly reduced activity against SARS-CoV-2 variants emerging in Brazil and South Africa that harbor mutations at positions 501, 484 and 417 in the S protein. Overall, the results provide insight into the dynamics, durability, and functional properties of the human B cell response to SARS-CoV-2 infection and have implications for the design of immunogens that preferentially stimulate protective B cell responses.”
The study findings were published in the peer reviewed journal: Science Immunology. https://immunology.sciencemag.org/content/6/56/eabg6916
Dr Mrunal Sakharkar and his colleagues profiled spike protein-specific B cell and antibody responses in 8 patients with mild and severe COVID-19 over five months.
Similar with previous findings, the study team observed a significant decline in neutralizing antibody levels in the blood over time; however, levels of spike protein-specific memory B cells remained stable or even increased during the same time frame.
Also, over the course of 120 days, monoclonal antibodies isolated from these B cells underwent increased somatic hypermutation, binding affinity, and neutralization potency - all signs of persistent B cell activity.
The study team also observed cross-neutralizing B cell populations, but these comprised just a small fraction of the B cell repertoire and were not prominent in the neutralizing response to SARS-CoV-2.
However a rather large proportion of the neutralizing antibody response only targeted conserved epitopes shared between SARS-CoV-2 and SARS-CoV and did not efficiently recognize emerging SARS-CoV-2 variants from Brazil and South Africa that harbor mutations at amino acid positions 417 and 484 of the spike protein.
Hence the study team suggests careful monitoring of circulating SARS-CoV-2 variants for variability in these protein sites to determine how these mutations impact vaccine-induced immunity.
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