Studies suggest that serum-positive individuals produce anti-SARS-CoV-2 antibodies with improved potency and breadth

Twenty months have passed since the 2019 coronavirus disease (COVID-19) pandemic began, 243 million people were infected, 4.94 million died, and 6.3 billion vaccines were given. rice field.

study: Hybrid immunity improves B cells and antibodies against SARS-CoV-2 mutants.. Image Credit: Kateryna Kon / Shutterstock

Many studies have so far protected against infection Neutralizing antibody Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) against spike (S) protein. NS Spike protein A metastable trimer class 1 fusion Glycoprotein It consists of S1 and S2 subunits. After binding to the human angiotensin converting enzyme 2 (ACE2) receptor and heparan sulfate on the cell surface, it mediates the invasion of the virus into the host cell.

Strong neutralizing antibodies produced after vaccination recognize the S1 subunit of each monomer, including receptor-binding domain (RBD) and N-terminal domain (NTD) immune-dominant sites. The majority of neutralizing antibodies have been shown to bind to the receptor binding motif (RBM) within the RBD, with a smaller fraction targeting the NTD. Neutralizing antibodies are very ineffective against the S2 subunit.

Understanding the molecular mechanism of the immune response to vaccination is essential because delta variants are the major causative agent behind breakthrough infections in fully vaccinated individuals.

Researchers isolated single cells with and without pre-infection of SARS-CoV-2 vaccinated with BNT162b2 mRNA and compared the nature of the neutralizing antibody response to the original Wuhan virus and subsequent variants. Did.The study was published in the latest issue of Nature..

Details of the study

The researchers enrolled 10 donors vaccinated with the BNT162b2 mRNA vaccine, 5 of whom were healthy people naive to SARS-CoV-2 infection at the time of enrollment. At the same time, the other five had been infected in the past and were in recovery.

Plasma analysis of these individuals showed that seropositive increased 2.46-fold in S protein-specific CD19 + CD27 + IgDIgM-memory B cells (important for providing MBC-humoral immunity) compared to seronegative, CD19. It shows that the level of + has increased overall. CD27 + IgDIgM- MBC 10%. Plasma from serum-positive individuals showed higher binding activity to the S protein and all tested domains than serum-negative individuals.

Post-vaccination neutralizing antibodies (nAbs) were isolated and analyzed using a cell sorting assay. Almost 6000 cells were sorted. More than 3000 produced monoclonal antibodies against peplomers and more than 400 neutralized the original Wuhan SARS-coronavirus. 411 nAbs were isolated, 71 of which were derived from seronegative and 340 from which were seropositive. The overall proportion of nAb-producing S protein-specific B cells was 7.5% in serum-negative individuals and 14.8% in serum-positive individuals.

Serum-positive individuals had a higher overall rate of mutant-neutralizing nAb than serum-negative individuals. The average frequency of nAb from seropositive neutralizing alpha, beta, and gamma mutants was 80.6 (n = 274) and 39.4 (n, respectively) compared to 70.4 (n = 50) and 22.5 (n = 50). = 134), 62.0% (n = 211). For serum negative, n = 16) and 43.6% (n = 31), respectively.

Further characterizing the breadth of coverage for these nAb variants, serum-positive individuals make up 71.0%, 62.5%, 23.7%, 22.8%, and 53.1% of the total nAb repertoire, whereas serum-negative donors. The nAb from was 48.1%. , Wuhan SARS-CoV-2 virus and alpha, beta, gamma, delta variants, 38.5%, 17.3%, 17.3%, 34.6%, respectively.

Overall, B.1.351 (beta) and B.1.1.248 (gamma) variants have been shown to escape nearly 70% of neutralizing antibodies. At the same time, a much smaller portion was affected by the B.1.1.7 (alpha) and B.1.617.2 (delta) variants. The overall loss of neutralization was always significantly higher with antibodies from naive people. This was also partly due to IGHV2-5. The IGHJ4-1 germline was found only in convalescent people and produced strong, widespread neutralizing antibodies.

Impact on research

The study showed that a third round of antibody production in the body could boost immunity to the most toxic SARS-CoV-2 mutants. This means that people who have not been pre-exposed to the virus can benefit significantly from the third vaccination. This helps prevent breakthrough infections and helps scientists prescribe better, stronger vaccines and contain the disease.