Findings of new study may help inform the design of next-generation COVID-19 vaccines, as new variants emerge

The researchers profiled patients with mild and severe COVID-19 over a period of five months.

“We collected longitudinal serum and peripheral blood mononuclear cell (PBMC) samples from a cohort of eight COVID-19 convalescent donors who experienced severe or mild disease. ​

“The first blood sample was drawn around 35.5 days following the onset of symptoms to allow for an assessment of the early B cell response to SARS-CoV-2 infection. The second and third blood samples were collected at around 95.5- and 153.5-days post-symptom onset, respectively, to evaluate the long-lived memory B cell response.”​

Results from the academia-industry research collaboration​​ show that, serum neutralizing antibody (nAb) responses waned rapidly but spike (S)-specific IgG+ memory B cells (MBCs), contrary to previous hypotheses, remain stable and continue to evolve over a five-month period, many months after the initial period of active viral replication.

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, said the scientists.

B cell immunodominance hierarchies were similar across donor repertoires and remained relatively stable as the immune response progressed.

The authors also noted that cross-reactive B cell populations, likely recalled 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. Thus, the authors suggest careful monitoring of circulating SARS-CoV-2 variants for variability in these protein sites to determine how these mutations impact vaccine-induced immunity.

Designing next-generation COVID-19 vaccines and therapies

The findings, say Mrunal Sakharkar and colleagues, 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.

Although vaccines have been developed and deployed at an unprecedented pace, the protection afforded by these vaccines may be short-lived due to waning serum antibody titers and/or the emergence of SARS-CoV-2 strains that evade vaccine-induced immunity, they added.

A detailed characterization of B cell responses induced by natural infection will provide key insights into the durability and breadth of protective immune responses and may facilitate the design of next-generation COVID-19 vaccines and therapies, said the team.

“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.”​

Source: Science Immunology​

Title: Prolonged evolution of the human B cell response to SARS-CoV-2 infection​

DOI: 10.1126/sciimmunol.abg6916​​

Authors: Sakharkar et al