The majority of the population can produce neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in severe cases of coronavirus disease 2019 (COVID-19), according to a study published February 11 in the open-access journal PLOS Pathogens by Michael Mor of Tel Aviv University, and colleagues. Moreover, the results support the use of combination antibody therapy to prevent and treat COVID-19.
The COVID-19 pandemic, caused by SARS-CoV-2, has had a profound impact on global public health.
Neutralizing antibodies that specifically target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein are thought to be essential for controlling the virus.
RBD-specific neutralizing antibodies have been detected in convalescent patients – those who have recovered from COVID-19. Some of the recoverees tend to have robust and long-lasting immunity, while others display a waning of their neutralizing antibodies.
The factors associated with an effective, durable antibody response are still unclear.
To address this gap in knowledge, Mor and colleagues used molecular and bioinformatics techniques to compare B-cell responses in eight patients with severe COVID-19 and 10 individuals with mild symptoms, 1.5 months after infection. Very ill patients showed higher concentrations of RBD-specific antibodies and increased B-cell expansion.
Among 22 antibodies cloned from two of these patients, six exhibited potent neutralization against SARS-CoV-2.
Bioinformatics analysis suggests that most people would be capable of readily producing neutralizing antibodies against SARS-CoV-2 in severe cases of COVID-19. Moreover, combinations of different types of neutralizing antibodies completely blocked the live virus from spreading.
According to the authors, these antibody cocktails can be further tested in clinical settings as a useful means to prevent and treat COVID-19.
“Even with a vaccine at our doorstep, arming clinicians with specific anti-SARS-CoV-2 therapeutics is extremely important,” the authors add.
“Combinations of neutralizing antibodies represent a promising approach towards effective and safe treatment of severe COVID-19 cases, especially in the elderly population or chronically ill people, who will not be able to so easily produce these antibodies upon infection or vaccination.”
Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious disease that has resulted in widespread global morbidity and mortality.
Humans make SARS-CoV-2–specific antibodies, CD4+ T cells, and CD8+ T cells in response to SARS-CoV-2 infection (1–4). Studies of acute and convalescent COVID-19 patients have observed that T cell responses are associated with reduced disease (5–7), suggesting that SARS-CoV-2–specific CD4+ T cell and CD8+ T cell responses may be important for control and resolution of primary SARS-CoV-2 infection.
Ineffective innate immunity has been strongly associated with a lack of control of primary SARS-CoV-2 infection and a high risk of fatal COVID-19 (8–12), accompanied by innate cell immunopathology (13–18). Neutralizing antibodies have generally not correlated with lessened COVID-19 disease severity (5, 19, 20), which was also observed for Middle Eastern respiratory syndrome (MERS), caused by MERS-CoV (21).
Instead, neutralizing antibodies are associated with protective immunity against secondary infection with SARS-CoV-2 or SARS-CoV in nonhuman primates (3, 22–25). Passive transfer of neutralizing antibodies in advance of infection (mimicking preexisting conditions upon secondary exposure) effectively limits upper respiratory tract (URT) infection, lower respiratory tract (lung) infection, and symptomatic disease in animal models (26–28).
Passive transfer of neutralizing antibodies provided after initiation of infection in humans has had more limited effects on COVID-19 (29, 30), consistent with a substantial role for T cells in control and clearance of an ongoing SARS-CoV-2 infection. Thus, studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner is likely important for understanding the durability of protective immunity against COVID-19 generated by primary SARS-CoV-2 infection (1, 19, 31).
Whereas sterilizing immunity against viruses can only be accomplished by high-titer neutralizing antibodies, successful protection against clinical disease or death can be accomplished by several other immune memory scenarios. Possible mechanisms of immunological protection can vary according to the relative kinetics of the immune memory responses and infection.
For example, clinical hepatitis after hepatitis B virus (HBV) infection is prevented by vaccine-elicited immune memory even in the absence of circulating antibodies, because of the relatively slow course of HBV disease (32, 33). The relatively slow course of severe COVID-19 in humans [median 19 days post–symptom onset (PSO) for fatal cases (34]) suggests that protective immunity against symptomatic or severe secondary COVID-19 may involve memory compartments such as circulating memory T cells and memory B cells (which can take several days to reactivate and generate recall T cell responses and/or anamnestic antibody responses) (19, 21, 31).
Immune memory, from either primary infection or immunization, is the source of protective immunity from a subsequent infection (35–37). Thus, COVID-19 vaccine development relies on immunological memory (1, 3). Despite intensive study, the kinetics, duration, and evolution of immune memory in humans to infection or immunization are not in general predictable on the basis of the initial effector phase, and immune responses at short time points after resolution of infection are not very predictive of long-term memory (38–40). Thus, assessing responses over an interval of 6 months or more is usually required to ascertain the durability of immune memory.
A thorough understanding of immune memory to SARS-CoV-2 requires evaluation of its various components, including B cells, CD8+ T cells, and CD4+ T cells, as these different cell types may have immune memory kinetics that are relatively independent of each other. Understanding the complexities of immune memory to SARS-CoV-2 is key to gaining insights into the likelihood of durability of protective immunity against reinfection with SARS-CoV-2 and secondary COVID-19 disease.
In this study, we assessed immune memory of all three branches of adaptive immunity (CD4+ T cell, CD8+ T cell, and humoral immunity) in a predominantly cross-sectional study of 188 recovered COVID-19 cases, extending up to 8 months after infection. The findings have implications for immunity against secondary COVID-19, and thus the potential future course of the pandemic (41, 42).
reference link: https://science.sciencemag.org/content/371/6529/eabf4063
More information: Mor M, Werbner M, Alter J, Safra M, Chomsky E, Lee JC, et al. (2021) Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors. PLoS Pathog 17(2): e1009165. doi.org/10.1371/journal.ppat.1009165
