Immunity against SARS-CoV-2 can last more than six months through antibody evolution and B-cell memory

With the 2019 coronavirus disease (COVID-19) pandemic infecting more than 52.7 million people worldwide and killing more than 1.2 million, a large amount of research has sought to better understand the Immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes COVID-19.

A research team from the Howard Hughes Medical Institute, USA, has studied the evolution of antibodies that fight against SARS-CoV-2 infection. Their study titled “Evolution of Antibody Immunity to SARS-CoV-2” was posted on the preprint server. bioRxiv*.

Background

SARS-CoV-2 infection triggers the development of antibodies that can neutralize the virus antigens, particularly the spike protein that the virus uses to enter host cells. Thus, they protect an individual from re-infection. The levels of antibodies developed against the infection can vary between people and, over time, the levels of antibodies also decrease. However, immune system B cells have a specific type called memory B cells. These memory B cells may be “called upon to produce antibodies upon reinfection,” the researchers suggest. This type of immune response is called a humoral memory response.

This use of memory B cells and their robustness in preventing reinfection has yet to be explored, the team explains.

Study design

For this study, the team of researchers analyzed the humoral memory response among 87 people. The humoral antibody response of the participants was studied at 1.3 months and 6.2 months after their infection with SARS-CoV-2. Nussenzweig, an immunologist at Rockefeller University in New York City and a collaborator on the research project, explains: “Our idea was that if we could find such neutralizing antibodies, we would know which part of the virus the vaccines should target. “

recommendations

Overall, the study results were:

Antibodies decrease over time

• Antibody responses to SARS-CoV-2 were found around 1.3 months or 40 days after infection.
• Plasma IgM, IgG and IgA anti-RBD (receptor-binding domain) antibodies decreased between 1.3 and 6.2 months after recovery from infection.
• The IgM antibody type showed the greatest decrease in anti-RBD reactivity (53 percent), followed by IgG (33 percent), while IgA decreased only 15 percent
• Those patients who had prolonged symptoms had significantly higher anti-RBD IgG and anti-N antibody levels at both time points.
• Although RBD antibodies and plasma neutralizing activity are significantly decreased, they were still detectable 6.2 months after infection in most patients.

Memory B cells

• Antibody levels in plasma decreased over time, but memory B cells were found to contribute to the immune response later after recovery
• To do this, the team used flow cytometry to isolate B cells that contained receptors that bound to RBD.
• Memory B cells that bound to RBD increased significantly between 1.3 and 6.2 months
• The authors wrote: “We conclude that while the magnitude of the RBD-specific memory B-cell compartment is preserved between 1.3 and 6.2 months after SARS-CoV-2 infection, there is a significant clonal turnover and an evolution of the antibody sequence … “

Antibody evolution

• The evolution of antibodies occurs due to a mutation in the germinal centers. Here, the virus antigen is retained in the form of immune complexes. These complexes of antigens and antibodies are found on the surface of follicular dendritic cells for a long time.
• Viruses that remain in the body after recovery act as a source of viral antigens for antibodies to develop. They may be present in the gut, the team found.
• Electron tomography and other methods helped find these residual viruses.
• Mutations were low in antibodies generated shortly after recovery from infection, the team noted.
• The team writes: “The anti-SARS-CoV-2 memory B-cell response evolves during the first 6 months after infection …”

Plots of circuses and specific B cells of RBD positive for IgG a, Sequences of the six individuals with clonal relationships represented. Interconnection lines indicate the relationship between antibodies that share V and J gene segment sequences in both IGH and IGL. The purple, green, and gray lines connect clones, clones, and related singles to each other, respectively. b, For each patient, the number of IgG heavy chain sequences (black) analyzed from six individuals at month 694 1.3 (left panel) or month 6.2 after infection (right panel). The number in the inner circle indicates the number of cells that were ordered for each individual indicated above the circle. c, The same as b but showing the combined data of the 6 patients. d, Comparison of the percentage of IgG positive B cells from six individuals at month 1.3 or at month 6.2 after infection. Horizontal bars indicate the mean. Statistical significance was determined by the paired t test.

Conclusions and consequences

The researchers found that “memory responses are responsible for protection against reinfection and are essential for effective vaccination.” This evolution of memory B cells occurs between 1.3 and 6.2 months after infection. With the persistent presence of antigens in the form of residual virus, antibodies continue to evolve.

Nussenzweig, said in a statement, “The very good news is that it is highly unlikely that infected people will become ill again for at least six months.” Christian Gaebler, another researcher on the project, said that “our results showed that it is not difficult for our immune system to produce effective antibodies against SARS-CoV-2.” He was also talking about his previous study published in the journal. Nature, in June of this year (2020).

“One of the things that people worry a lot about is what will happen in six months or a year,” Nussenzweig said. “Will people who have recovered from COVID-19 still be protected?” This study shows that the answer may be “yes,” especially for those who had a persistent presence of the virus in their bodies, particularly in the gut, the researchers say.

*Important news

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or be treated as established information.