scholarly journals BCG Vaccine Derived Peptides Induce SARS-CoV-2 T Cell Cross-Reactivity

2021 ◽  
Vol 12 ◽  
Author(s):  
Peter J. Eggenhuizen ◽  
Boaz H. Ng ◽  
Janet Chang ◽  
Ashleigh L. Fell ◽  
Rachel M. Y. Cheong ◽  
...  

Epidemiological studies and clinical trials suggest Bacillus Calmette-Guérin (BCG) vaccine has protective effects against coronavirus disease 2019 (COVID-19). There are now over 30 clinical trials evaluating if BCG vaccination can prevent or reduce the severity of COVID-19. However, the mechanism by which BCG vaccination can induce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses is unknown. Here, we identify 8 novel BCG-derived peptides with significant sequence homology to either SARS-CoV-2 NSP3 or NSP13-derived peptides. Using an in vitro co-culture system, we show that human CD4+ and CD8+ T cells primed with a BCG-derived peptide developed enhanced reactivity to its corresponding homologous SARS-CoV-2-derived peptide. As expected, HLA differences between individuals meant that not all persons developed immunogenic responses to all 8 BCG-derived peptides. Nevertheless, all of the 20 individuals that were primed with BCG-derived peptides developed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2-derived peptides. These findings provide an in vitro mechanism that may account, in part, for the epidemiologic observation that BCG vaccination confers some protection from COVID-19.

2020 ◽  
Author(s):  
Peter J. Eggenhuizen ◽  
Boaz H. Ng ◽  
Janet Chang ◽  
Ashleigh L. Fell ◽  
Wey Y. Wong ◽  
...  

AbstractEpidemiological studies suggest that the Bacillus Calmette-Guérin (BCG) vaccine may have protective effects against coronavirus disease 2019 (COVID-19); and, there are now more than 15 ongoing clinical trials seeking to determine if BCG vaccination can prevent or reduce the severity of COVID-19 (1). However, the mechanism by which BCG vaccination can induce a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific T cell response is unknown. Here, in silico, we identify 8 BCG derived peptides with significant sequence homology to either SARS-CoV-2 NSP3 or NSP13 derived peptides. Using an in vitro co-culture system, we show that human CD4+ and CD8+ T cells primed with a BCG derived peptide developed enhanced reactivity to its corresponding SARS-CoV-2 derived peptide. As expected, HLA differences between individuals meant that not all persons developed immunogenic responses to all 8 BCG derived peptides. Nevertheless, all of the 20 individuals that were primed with BCG derived peptides developed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2 derived peptides. These findings provide a mechanistic basis for the epidemiologic observation that BCG vaccination confers protection from COVID-19; and supports the use of BCG vaccination to induce cross-reactive SARS-CoV-2 specific T cell responses.


2021 ◽  
Author(s):  
Ricardo da Silva Antunes ◽  
Suresh Pallikkuth ◽  
Erin Williams ◽  
Esther Dawen Yu ◽  
Jose Mateus ◽  
...  

AbstractHerein we measured CD4+ T cell responses against common cold corona (CCC) viruses and SARS-CoV-2 in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC reactive T cells in SARS-CoV-2 seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses is consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC reactivity was decreased in SARS-CoV-2 infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego.


Allergy ◽  
2017 ◽  
Vol 73 (1) ◽  
pp. 221-229 ◽  
Author(s):  
C.-y. Lin ◽  
C.-W. Wang ◽  
C.-Y. R. Hui ◽  
Y.-C. Chang ◽  
C.-H. Yang ◽  
...  

Author(s):  
Ricardo da Silva Antunes ◽  
Suresh Pallikkuth ◽  
Erin Williams ◽  
Dawen Yu Esther ◽  
Jose Mateus ◽  
...  

Abstract Herein we measured CD4 + T cell responses against common cold corona (CCC) viruses and SARS-CoV-2 in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC reactive T cells in SARS-CoV-2 seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 T cell reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses is consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC T cell reactivity was decreased in SARS-CoV-2 infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego.


2002 ◽  
Vol 11 (4) ◽  
pp. 669-674 ◽  
Author(s):  
S. Carlens ◽  
D. Liu ◽  
O. Ringdén ◽  
J. Aschan ◽  
B. Christensson ◽  
...  

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4543-4543 ◽  
Author(s):  
T. Buanes ◽  
S. Bernhardt ◽  
K. Lislerud ◽  
I. Gladhaug ◽  
M. Moeller ◽  
...  

4543 Background: K-RAS mutations are found in most adenocarcinoma of the pancreas, and targeting mutant RAS by vaccination may be of clinical importance. The present follow-up study was performed to determine whether or not mutant RAS specific T cells were still present in long term survivors seven to nine years after postoperative adjuvant vaccination with synthetic mutant RAS peptides Methods: During 1995–98, all together 23 patients were recruited into two clinical studies. The patients in CTN95002 (n = 10) were given a single mutant RAS peptide (100μg) corresponding to the RAS mutation identified in the patient’s tumor. Patients in CTN98010 (n = 13) were given a mixture of seven mutant RAS peptides, (700μg), corresponding to the most common mutations in pancreatic adenocarcinoma, in a 10 week vaccination regimen, using GM-CSF as an adjuvant, and boosters for an extended period. Immune responses were measured as skin reaction (DTH) and/or in vitro T-cell response. Blood samples from the five patients, still alive in 2006, were investigated by in vitro T-cell proliferation assay for immunological memory. Results: The five surviving patients were all immune responders during the primary vaccination period. Analysis of T-cell reactivity was performed seven (one patient), eight (one patient) and nine years (three patients) after resection/vaccination. Three patients still showed immune responses against the vaccine given previously. T cell reactivity against the Gly12Val mutation was observed in one patient receiving this peptide. In another patient a strong T cell reactivity against all seven peptides present in the vaccine, was observed. Conclusions: Long term survival beyond seven to nine years was only found in patients who primarily responded immunologically on the RAS-vaccination. Long term immunological memory can be induced by peptide vaccination. No significant financial relationships to disclose.


2020 ◽  
Author(s):  
Sandip D. Kamath ◽  
Sandra Scheiblhofer ◽  
Christopher M. Johnson ◽  
Yoan Machado ◽  
Thomas McLean ◽  
...  

AbstractBackgroundTropomyosins are highly conserved proteins, an attribute that forms the molecular basis for their IgE antibody cross-reactivity. Despite structural similarities, their allergenicity varies greatly between ingested and inhaled invertebrate sources. In this study, we investigated the relationship between the structural stability of different tropomyosins, their endolysosomal degradation patterns and T-cell reactivity.MethodsWe investigated the differences between four tropomyosins - the major shrimp allergen Pen m 1 and the minor allergens Der p 10 (dust mite), Bla g 7 (cockroach) and Ani s 3 (fish parasite) - in terms of IgE binding, structural stability, endolysosomal degradation and subsequent peptide generation, and T-cell cross-reactivity in a BALB/c murine model.ResultsDespite their conserved primary structure and consequent IgE co-reactivity, the invertebrate tropomyosins displayed different protein stabilities. Pen m 1 and Ani s 3, but not Der p 10 and Bla g 7 elicited differential melting temperatures that were pH-dependent. Endolysosomal experiments demonstrated differential degradation, as a function of stability, generating different peptide repertoires. Pen m 1 T-cell clones, with specificity for sequences highly conserved in all four tropomyosins, did not proliferate with Der p 10, Bla g 7 and Ani s 3, indicating that these peptides were not naturally produced for other invertebrate tropomyosins.ConclusionsOur data suggest that, although invertebrate tropomyosins exhibit a high degree of IgE cross-reactivity due to conserved B-cell epitopes, they do not necessarily share identical cross-reactive T-cell epitopes. This is likely due to differential endolysosomal processing as a function of different structural stabilities.


Author(s):  
Soheila Alyasin ◽  
Zahra Kanannejad ◽  
Hossein Esmaeilzadeh ◽  
Hesamedin Nabavizadeh ◽  
Mohammad Amin Ghatee ◽  
...  

Bacillus Calmette Guerin (BCG) was designed for protecting children against tuberculosis. Also, it can protect against other infectious diseases through the induction of trained immunity. Due to its heterologous protective effects, the BCG vaccine has been proposed as a treatment option for coronavirus disease-2019 (COVID-19). Epidemiological studies have found that countries without BCG vaccination policy have experienced higher mortality rates related to COVID-19 infection than those with BCG vaccination policy. However, there are some confounding factors such as age, population intensity, immigration, the pandemic phase, and data accuracy that may affect these results. Therefore, this hypothesis should be evaluated by clinical trial studies. Large-scale clinical trials are in progress to investigate if the BCG vaccine could be used as a useful tool for protection against COVID-19 infection.


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