Reaction of SARS-CoV-2 antibodies with other pathogens, vaccines, and food antigens

Abstract

It has been shown that SARS-CoV-2 shares homology and cross-reacts with vaccines, other viruses, common bacteria and many human tissues. We were inspired by these findings, firstly, to investigate the reaction of SARS-CoV-2 monoclonal antibody with different pathogens and vaccines, particularly DTaP. Additionally, since our earlier studies have shown immune reactivity by antibodies made against pathogens and autoantigens towards different food antigens, we also studied cross-reaction between SARS-CoV-2 and common foods. For this, we reacted monoclonal and polyclonal antibodies against SARS-CoV-2 spike protein and nucleoprotein with 15 different bacterial and viral antigens and 2 different vaccines, BCG and DTaP, as well as with 180 different food peptides and proteins. The strongest reaction by SARS-CoV-2 antibodies were with DTaP vaccine antigen, E. faecalis, roasted almond, broccoli, soy, cashew, α+β casein and milk, pork, rice endochitinase, pineapple bromelain, and lentil lectin. Because the immune system tends to form immune responses towards the original version of an antigen that it has encountered, this cross-reactivity may have its advantages with regards to immunity against SARS-CoV-2, where the SARS-CoV-2 virus may elicit a "remembered" immune response because of its structural similarity to a pathogen or food antigen to which the immune system was previously exposed. Our findings indicate that cross-reactivity elicited by DTaP vaccines in combination with common herpesviruses, bacteria that are part of our normal flora such as E. faecalis, and foods that we consume on a daily basis should be investigated for possible cross-protection against COVID-19. Additional experiments would be needed to clarify whether or not this cross-protection is due to cross-reactive antibodies or long-term memory T and B cells in the blood.

Keywords: SARS-CoV-2; antibodies; food antigens; molecular mimicry; pathogens; vaccines.

Figure 1

Reaction of human SARS-CoV-2 spike protein monoclonal antibody with spike protein and different bacterial and viral antigens, including DTaP and BCG vaccines. At 3SD above the OD of background or 0.27, significant reaction between spike protein antibody and bacterial and viral antigens was observed. Each determination of antigen-antibody reaction was performed in quadruplicate. The standard deviations (SDs) for all the reactions were less than 0.1, and are shown as error bars. In these experiments, when monoclonal anti-SARS-CoV-2 antibodies were replaced with sera from healthy subjects, non-significant reactions with a mean of 0.25 were observed from the sera with spike protein. Percentages of significant reactivity are shown. DTaP is shown to be the most reactive. * = Antigens whose reactions were under the cutoff and/or close to the blank.

Figure 2

Reaction of human SARS-CoV-2 nucleoprotein monoclonal antibody with nucleoprotein and different bacterial and viral antigens, including DTaP and BCG vaccines. At 3SD above the OD of background or 0.3, significant reaction between spike protein antibody and bacterial and viral antigens was observed. Each determination of antigen-antibody reaction was performed in quadruplicate. The SDs for all the reactions were less than 0.12, and are shown as error bars. In these experiments, when monoclonal anti-SARS-CoV-2 antibodies were replaced with sera from healthy subjects, non-significant reactions with a mean of 0.29 were observed from the sera with nucleoprotein. The ODs of these reactions were lower than 0.3. Percentages of significant reactivity are also shown. DTaP is shown to be the most reactive. * = Antigens whose reactions were under the cutoff and/or close to the blank.

Figure 3

Reaction of human SARS-CoV-2 spike protein monoclonal antibody with various food antigens. At 3SD above the OD of antibody reaction with non-reactive foods or OD of 0.56, the spike protein antibody reacted significantly with 28 out of 180 tested food proteins and peptides. These reactions of SARS-CoV-2 spike protein antibody with different food antigens was obtained from quadruplicate testing. The SDs for all the reactions were less than 0.1, and are shown as error bars. * = Antigens whose reactions were under the cutoff and/or close to the blank. Glia Tox Pep, Gliadin Toxic Peptide; Peanut Agg, Peanut Agglutinin; Soy Bean Agg, Soy Bean Agglutinin; Bean Agg, Bean Agglutinin; Pineapple Br, Pineapple Bromelain; Ck, Cooked.

Figure 4

Reaction of human SARS-CoV-2 nucleoprotein monoclonal antibody with various food antigens. At 3SD above the OD of antibody reaction with non-reactive foods or OD of 0.64, the nucleoprotein antibody reacted significantly with 26 out of 180 tested food proteins and peptides. The data was obtained from quadruplicate testing. The SDs for all the reactions were less than 0.1, and are shown as error bars. * = Antigens whose reactions were under the cutoff and/or close to the blank. Glia Tox Pep, Gliadin Toxic Peptide; Peanut Agg, Peanut Agglutinin; Soy Bean Agg, Soy Bean Agglutinin; Bean Agg, Bean Agglutinin; Pineapple Br, Pineapple Bromelain; Rice Endo, Rice Endochitinase; Ck, Cooked.

Figure 5

Reaction of human SARS-CoV-2 spike protein monoclonal antibody with different bacterial, viral and food antigens at dilutions of 1:200 , 1:400 , and 1:800 . Note that in proportion to the dilution of the antigens, a significant decline in antibody-antigen reaction is observed. Each determination of antibody-antigen reaction was performed in triplicate. The SDs for all the reactions were less than 0.1, and are shown as error bars.

Figure 6

Reaction of human SARS-CoV-2 nucleoprotein monoclonal antibody with different bacterial, viral and food antigens at dilutions of 1:200 , 1:400 , and 1:800 . Note that in proportion to the dilution of the antigens, a significant decline in antibody-antigen reaction is observed only in the antigens with ODs that are >0.5. Each determination of antibody-antigen reaction was performed in triplicate. The SDs for all the reactions were 0.1 or less, and are shown as error bars. .

Figure 7

Reaction of affinity-purified rabbit polyclonal antibodies made against different food antigens with recombinant SARS-CoV-2 spike or nucleoprotein . Each determination of antigen-antibody reaction was performed in quadruplicate. The SDs for all the reactions were 0.1 or less, and are shown as error bars. * = Antigens whose reactions were under the cutoff and/or close to the blank. WGA, Wheat Germ Agglutinin; Peanut Agg, Peanut Agglutinin; Soy Agg, Soy Agglutinin; PHA, Phytohemagglutinin. Percentages of significant reactivity are also shown.

Figure 8

Reaction of human sera with low (Negative) or high levels of IgG antibody against EBV-EAD, HSV 1 + 2, HHV-6 and different food antigens with SARS-CoV-2 spike protein-coated plates. Black bars = means.