How important is sterilization of immunity in protection against SARS-CoV-2?

How important is sterilization of immunity in protection against SARS-CoV-2?

In a recent article published in Immunity, The authors discussed the underlying principles of sterilizing immunity and its importance in protecting individuals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections during the coronavirus disease 2019 (COVID-19) pandemic. ).

Study: Sterilizing Immunity: Understanding COVID-19.  Image Credit: nobeastsofierce/Shutterstock
To study: Sterilizing Immunity: Understanding COVID-19. Image Credit: nobeastsofierce/Shutterstock


During an infection, B and T cells of the immune system mount an adaptive immune response by secreting serum antibodies and killing infected host cells, respectively. Although serum antibody levels decline after infection, bone marrow plasma cells continue to produce antigen-specific antibodies for a long time.

Upon re-encountering the same pathogen, memory B cells developed during the previous infection can rapidly increase antibody titers against the pathogen. The immune response generated by plasma cells and memory B cells during reinfection is much more powerful and rapid, often eliminating the pathogen before the disease becomes symptomatic or severe.

However, with viruses, the second encounter is often with a mutated variant of the previous virus, making it difficult for the high-affinity antibodies formed by the memory immune response to recognize and neutralize the pathogen.

Sterilizing immunity

Sterilizing immunity prevents the pathogen from infecting the host by eliminating it before it can enter and replicate in the host cell, ideally at the site of entry. Since early reinfections are usually asymptomatic and low pathogen levels during reinfections under activity of memory immunity are difficult to detect, it is difficult to distinguish sterilizing immunity from protective immune memory. The absence of clearly defined parameters or correlates with the measurement of sterilizing immunity adds to the difficulty.

Vaccines present the immune system with attenuated pathogens or antigens consisting of structures on the surface of the pathogen to generate a mild adaptive immune response and a long-lasting memory immune response. Booster shots reintroduce the antigen to increase the memory response.

The affinity maturation process of antibodies generates variant antibodies mediated by random mutations, which exhibit better antigen binding. High-affinity antibodies developed through affinity maturation prevent viruses from invading host cells by binding to and blocking virus receptor sites on the host cell surface, mediating sterilizing immunity.

immune escape

Pathogens have evolved immune escape strategies to avoid host innate and adaptive immune responses and continue host-to-host transmission. Bacteria and parasites generate various antigens through changes in gene expression, while viruses mutate or carry out antigenic shift. Antigenic shift results in exchanges of genome fragments between two viruses that infect the same host cell. The diversity of antigens in pathogens reduces the efficacy of vaccines.

Antibody responses in the host cell also exert selection pressure, resulting in the survival and transmission of viruses that can survive the host cell’s immune response. However, antibodies that target conserved regions of the virus or other pathogen can effectively neutralize emerging variants of the pathogen. Broadly neutralizing antibodies are formed as part of the affinity maturation process, but the induction of broad neutralizing antibody responses by vaccines has proven difficult.

COVID-19 and sterilizing immunity

The absence of prior immunity to SARS-CoV-2 resulted in the rapid global spread of COVID-19 and led to severe outcomes, including high mortality worldwide. The worldwide push to develop vaccines has successfully limited the spread and severity of the disease.

Vaccines and antibody therapies have largely targeted the spike protein and receptor-binding domains of SARS-CoV-2. However, the emergence of SARS-CoV-2 variants that evade the immune system is a prime example of host-pathogen co-evolution, with emerging variants eliminating earlier strains and gaining global dominance.

However, memory responses developed from previous vaccines and infections with older variants successfully protect people against severe outcomes from COVID-19, even during infections with the new mutated variants. Studies indicate that this cross-protection is likely due to broadly neutralizing antibodies against the relatively conserved regions of the receptor-binding domain.

According to the authors, sterilizing immunity in the context of SARS-CoV-2 will be difficult to achieve unless vaccine- or infection-induced immunity generates broadly neutralizing antibodies or the rate of viral evolution is slowed. To inhibit viral invasion at the site of entry, humoral responses in the upper respiratory tract must be stronger, and vaccines have not been successful in eliciting potent immune responses in mucosal layers.


In summary, the authors discussed how booster vaccinations and pathogen exposure could elicit strong memory responses, establishing sterilizing immunity through broadly neutralizing antibodies produced by the affinity maturation process. However, the evolution of pathogens and the diversity of antigens challenge the achievement of sterilizing immunity.

The rapid transmission and large viral reservoirs of SARS-CoV-2 result in emerging immune evasion variants. The inability of COVID-19 vaccines to generate broadly neutralizing antibodies indicates that sterilizing immunity will be difficult to achieve in the context of SARS-CoV-2. However, cross-reactive immunity from previous vaccines and infections continues to exhibit some protection against serious infections from emerging variants.

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