Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causal agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, primarily causes mild to moderate upper-respiratory tract illness. However, some individuals with COVID-19 develop severe infections and require hospital admission.
Study: Reaction of SARS-CoV-2 antibodies with other pathogens, vaccines, and food antigens. Image Credit: Peddalanka Ramesh Babu / Shutterstock
Generally, when the body is exposed to different pathogens, it induces an immune response. Some of these immune cells, such as memory T and memory B cells, are retained by the body, which protects against similar pathogenic infections or exposure to cross-reactive antigens in the future. Moreover, these memory cells fight more effectively and efficiently, along with providing protection.
Immunologically, when humans encounter a new infection, the host's immune system activates memory T and B cells, which offer protection against a multitude of antigens via the production of protective and cross-reactive antibodies. For instance, due to cross-reactive antigen binding, pre-existing memory cells generated against the common cold virus protected against SARS-CoV-2 infection.
In the context of the recent pandemic, the memory T cells were able to detect many fragments of spike and non-spike regions of SARS-CoV-2. This observation was based on epitope similarities against a peptide pool of other coronaviruses. Due to pre-existing memory cells, some individuals experienced mild or moderate symptoms while others experienced severe infections. Hence, the memory T cells induced during infection caused by common cold coronaviruses are responsible for the massive heterogeneity in the human immune response to COVID-19.
Besides prior common cold infection, vaccination against various infections may also cause cross-reactivity to SARS-CoV-2. This might be why children vaccinated against different bacterial and viral antigens were not susceptible to SARS-CoV-2 infection. In addition, as immunity induced via these vaccines declines with age, the older population was deemed more prone to contract COVID-19 disease.
Although common herpesviruses were found to be a poor source of cross-reactivity, diphtheria, tetanus, and pertussis (DTaP) vaccine-induced significant cross-reactive immunity to SARS-CoV-2. Cross-reactivity also enhances the risk for autoimmunity, i.e., cross-reactivity between SARS-CoV-2 antigens and human tissue antigens. Antigenic mimicry between human autoantigens and dietary proteins was also reported.
About the Study
In a recent Frontiers in Immunology journal study, scientists analyzed how SARS-CoV-2 monoclonal antibodies interacted with different pathogens and vaccines, especially DTaP. Additionally, the cross-reactivity between SARS-CoV-2 proteins and common foods that are consumed daily was determined. This is important because when undigested food antigens enter the circulation system, they produce food-specific antibodies. The cumulative cross-reactive immunity induced by peptides and food antigens, as well as those elicited by vaccines, bacterial and viral infection may play an important role in protecting a body against a wide range of pathogens, including SARS-CoV-2.
Since the epitope shared between two proteins does not indicate immune-cross-reactivity, the current study utilized monoclonal antibodies specific to SARS-CoV-2. Human IgG monoclonal antibody made against SARS-CoV-2 spike protein's S1 domain and nucleoprotein were used. Rabbit polyclonal antibodies were used to analyze its reaction against different food antigens.
Mainly monoclonal antibodies were used in this study because they can detect one epitope per antigen and decrease the risk for cross-reactivity with other molecules. Additionally, monoclonal antibodies reduce the possibility of false positive cross-reactivity. Human SARS-CoV-2 nucleoprotein monoclonal antibodies were used as they could bind to the non-linear/conformational epitope of N protein of SARS-CoV-2 and SARS-CoV. This protein can also induce innate memory in human primary monocytes.
SARS-CoV-2 spike protein-specific antibodies were found to react most with the DTaP vaccine and, to a lesser degree, with E. faecalis bacteria, which is a common human gut microbe. A lesser reaction was observed against EBV Ab to Early Antigen D (EBV-EAD), EBV-Nuclear Antigen (EBNA) and B. burgdorferi. No reaction was observed against BCG, measles, E. coli CdT, EBV Viral Capsid Antigen Antibody (EBV-VCA), and Varicella-zoster virus (VZV).
Milk, gliadin toxic peptide, pea protein, α+β casein, soy, lentil lectin, and roasted almond were found to react with the SARS-CoV-2 spike protein antibody. Additionally, in the case of the SARS-CoV-2 nucleoprotein antibody, the strongest reaction was found with broccoli, soybean, pork, rice endochitinase, cashew, and gliadin toxic peptide.
The overall reaction of SARS-CoV-2 nucleoprotein monoclonal antibody with the DTaP vaccine was found to be most potent. In contrast, less strong reactions were observed with other vaccines and common viral and bacterial antigens, such as E. faecalis and herpesviruses. Surprisingly, no reaction was observed against BCG vaccine antigens. Many food proteins and peptides were found to share homology with SARS-CoV-2 proteins.
The current study's findings indicated that cross-reactivity induced via DTaP vaccines, along with common viruses (e.g., herpesviruses) and bacteria (e.g., E. faecalis, E. coli) protects against SARS-CoV-2 infection. Furthermore, the cross-reactivity between food antigens and different pathogens explains why most of the global population, repeatedly exposed to different SARS-CoV-2 variants, were not severely infected.