Examination of Homologies between COVID-19 Vaccines and Common Allergens: The Potential for T Cell-mediated Responses for Allergic Rhinitis and Asthma : Infectious Diseases & Immunity

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Examination of Homologies between COVID-19 Vaccines and Common Allergens: The Potential for T Cell-mediated Responses for Allergic Rhinitis and Asthma

Hartwell, Micah1,2,∗; Greiner, Benjamin H.3; Nicks, Savannah2

Author Information
Infectious Diseases & Immunity: October 2022 - Volume 2 - Issue 4 - p 282-284
doi: 10.1097/ID9.0000000000000056
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Abstract

Amid the COVID-19 pandemic, it is prudent to determine the potential connection between COVID-19 vaccines and the severity of allergic rhinitis and allergic asthma. Skevaki et al. established that infection from influenza A strain H1N1 in mice served as a mediating factor of severe complications of allergic disease, presenting virus-mediated T-cell cross-reactive responses as a potential protective mechanism in asthma.[1] In the aforementioned study, when presented with an allergen challenge designed to induce allergic airway inflammation, previous influenza infection in mice proved to mitigate future allergic airway reactions. Specifically, according to this study, mice previously infected with influenza experienced decreased mucus production, decreased production of inflammatory Th2 cytokines and thereby eosinophils, and an overall improvement in airway inflammation when presented with an aerosol challenge that historically provokes physiologic effects of asthma. Virus-specific memory T-cell cross-reactivity has previously been shown in other studies regarding pathogens[2,3]] and allergens,[4] linking autoimmune responses to certain protein sequences via molecular mimicry.[5]

Further, Balz et al. showed that the SARS-CoV-2 virus shares relatively large protein sequences homologous to grass pollens, dust mites, and molds,[6] thus post-infection, SARS-CoV-2 oriented T-cells may provide a mediated immune response to these allergens. In the context of allergic rhinitis and allergic asthma, an increasing pool of cross-reactive memory T-cells may play an important role in protection against T-cell-mediated chronic inflammation; however, induced immunopathology must also be considered.

Given the protective factor of COVID-19 vaccines against the virus and their mass distribution, our objective was to explore the potential overlap between the COVID-19 mRNA vaccines from Pfizer-BioNtech and Moderna and known allergens indexed through the University of Nebraska’s Food Allergy Research and Resource Program (FARRP) Allergen Protein Database (allergenonline.org) and the FASTA tool, using the BLOSUM50 scoring matrix as previously published.[7] Given the Codex Alimentarius Commission recommendation likelihood of cross-reactivity criteria, we reported allergens with 35% (or greater) similarity over segments of 80 amino acids (Criteria A) and those with short (8 or more amino acids) identical matches (Criteria B).

For the Pfizer vaccine, we identified one allergen meeting Criteria A, from pine nuts, and six that met Criterion B from Tufted Grass and Alternaria alternata, the most common fungal allergen associated with asthma [Table 1].[8] For the Moderna vaccine, we found 7 allergens meeting Criteria A and 12 that met Criteria B. Allergens meeting Criteria A included spreading pellitory (grass), lipocalin from guinea pigs, ragweed, wheat endosperm, sesame, and dust mites. Allergens that met Criteria B were Kentucky blue, cat, and Timothy grasses, and Penicillium crustosum (mold) [Table 2]. Both vaccines showed matching sequences (Criteria B) with perennial ryegrass.

Table 1 - Allergens with 35% (or greater) similarity over segments of 80 amino acids (Criteria A)
Allergen (species) Common name IUISa allergen NCBI reference no.b Highest % seq. ID Percent similarity (%)
Moderna
Parietaria judaica Spreading pellitory Par j 2.0102 1532056 32.40 85.30
Cavia porcellus Guinea pig Cav p 1.0102 1604536257 23.20 75.40
Ambrosia artemisiifolia Short ragweed Unassigned 291482308 50.00 74.10
Ambrosia artemisiifolia Ragweed Unassigned 291482310 44.40 62.50
Triticum aestivum Wheat Unassigned 21743 12.90 62.30
Sesamum indicum Sesame Ses i 3.0101 13183177 14.40 59.40
Dermatophagoides farinae Dust mites Der f 15.0101 5815436 17.20 57.10
Pfizer
Pinus koraiensis Pine nuts Pin k 2.0101 567773309 18.30 63.30
aColumn presents the systematic allergen nomenclature recognized by the International Union of Immunological Societies (IUIS; https://iuis.org/) and World Health Organization.
bThe National Center for Biotechnology Information (NCBI) reference no. is searchable within the United States National Library of Medicine's protein database (https://www.ncbi.nlm.nih.gov/protein/).

Table 2 - Allergens with ≥ 8 sequential amino acids match (Criteria B)
Allergen Common name IUISa allergen NCBI reference no. GI Classificationb
Moderna
 Penicillium crustosum Fungus Pen cr 26.0101 371537645
 Corylus avellana Hazelnut Cor a 13.0101 29170509
 Lolium perenne Perennial ryegrass Unassigned 4416516
 Lolium perenne Perennial ryegrass Unassigned 6634467
 Phleum pratense Timothy grass Unassigned 345108717
 Poa pratensis Kentucky bluegrass Unassigned 113560
 Poa pratensis Kentucky bluegrass Unassigned 113562
 Poa pratensis Kentucky bluegrass Unassigned 539056
 Poa pratensis Kentucky bluegrass Unassigned 113561
 Dactylis glomerata Orchard Unassigned 14423124
 Dactylis glomerata Orchard Unassigned 18093971
 Holcus lanatus Velvet grass Hol l 5.0101 2266625
Pfizer
 Lolium perenne Perennial ryegrass Unassigned 4416516
 Holcus lanatus Velvet grass Hol l 5.0101 2266625
 Alternaria alternata Fungus Alt a 5.0101 1850540
 Alternaria alternata Fungus Unassigned 1173071
 Davidiella tassiana Fungus Cla h 5.0101 5777795
 Fusarium culmorum Fungus Fus c 1.0101 19879657
aColumn presents the systematic allergen nomenclature recognized by the International Union of Immunological Societies (IUIS; https://iuis.org/) and World Health Organization.
bThe National Center for Biotechnology Information (NCBI) reference no. is searchable within the United States National Library of Medicine's protein database (https://www.ncbi.nlm.nih.gov/protein/).

T-cell mediated antigen cross-reactivity between viruses and allergens is a relatively new area of study in clinical immunology; a discipline that may be particularly useful regarding the SARS-CoV-2 virus and the allergic response in humans. Considering our findings of homologous overlap between known allergens and the Pfizer and Moderna vaccines, an altered T-cell mediated immune response may be observed in persons with allergic asthma and allergic rhinitis after vaccination, with Pfizer or Moderna mRNA vaccines, against SARS-CoV-2.

Our findings also contribute to the growing literature regarding the “old friends” hypothesis—persons exposed to infectious agents throughout childhood are less likely to experience histamine-mediated reactions to allergens.[9] While the previously mentioned correlations between influenza infections in mice models and allergic responses[1] support the heterologous immune reactivity theory, this study assessed the potential cross-reactivity among COVID-19 vaccines and common allergens. These results suggest that vaccination with the Pfizer-BioNtech and Moderna COVID-19 vaccines may contribute to T-cell cross-reactivity with allergens that impact allergic asthma and allergic rhinitis. Further research should assess the clinical implications of COVID-19 vaccination on the severity and symptomatology of the allergic disease, in addition to natural viral infection.

Limitations of the study were that only sequenced allergens within the FARRP database were analyzed, which may exclude other potential cross-reactive proteins. Further, these overlaps do not establish cross-reactivity—simply that it may exist. Additionally, the protein composition ratio and amino acid structural style may also play a role in this function. Further research is needed to establish evidence of allergen mediation, histamine activation, or reduction of asthma symptomatology after vaccination.

Acknowledgments

We would like to acknowledge and thank Dr. T. Kent Teague, from the University of Oklahoma School of Community Medicine, for providing guidance in our research and a critical review of our manuscript.

Conflicts of Interest

None.

References

1. Skevaki C, Hudemann C, Matrosovich M, et al. Influenza-derived peptides cross-react with allergens and provide asthma protection. J Allergy Clin Immunol 2018; 142(3):804–814. doi: 10.1016/j.jaci.2017.07.056.
2. McMaster SR, Gabbard JD, Koutsonanos DG, et al. Memory T cells generated by prior exposure to influenza cross react with the novel H7N9 influenza virus and confer protective heterosubtypic immunity. PLoS One 2015; 10(2):e0115725 doi: 10.1371/journal.pone.0115725.
3. Savic M, Dembinski JL, Kim Y, et al. Epitope specific T-cell responses against influenza A in a healthy population. Immunology 2016; 147(2):165–177. doi: 10.1111/imm.12548.
4. Shen ZT, Nguyen TT, Daniels KA, et al. Disparate epitopes mediating protective heterologous immunity to unrelated viruses share peptide–MHC structural features recognized by cross-reactive T cells. J Immunol 2013; 191(10):5139–5152. doi: 10.4049/jimmunol.1300852.
5. Sewell AK. Why must T cells be cross-reactive? Nat Rev Immunol 2012; 12(9):669–677. doi: 10.1038/nri3279.
6. Balz K, Kaushik A, Chen M, et al. Homologies between SARS-CoV-2 and allergen proteins may direct T cell-mediated heterologous immune responses. Sci Rep 2021; 11(1):4792 doi: 10.1038/s41598-021-84320-8.
7. Abdelmoteleb M, Zhang C, Furey B, et al. Evaluating potential risks of food allergy of novel food sources based on comparison of proteins predicted from genomes and compared to www.AllergenOnline.org. Food Chem Toxicol 2021; 147:111888 doi: 10.1016/j.fct.2020.111888.
8. Salo PM, Arbes SJ Jr, Sever M, et al. Exposure to Alternaria alternata in US homes is associated with asthma symptoms. J Allergy Clin Immunol 2006; 118(4):892–898. doi: 10.1016/j.jaci.2007.12.1164.
9. Rook GA. Regulation of the immune system by biodiversity from the natural environment: an ecosystem service essential to health. Proc Natl Acad Sci U S A 2013; 110(46):18360–18367. doi: 10.1073/pnas.1313731110.
Keywords:

Rhinitis, allergic; Allergy; COVID-19; Cross-reactivity; mRNA; Vaccines

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