Are There Hidden Genes in DNA/RNA Vaccines?
Due to the fast global spreading of the Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2), prevention and treatment options are direly needed in order to control infection-related morbidity, mortality, and economic losses. Although drug and inactivated and attenuated virus vaccine devel...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-02-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.801915/full |
| _version_ | 1819284501382037504 |
|---|---|
| author | Christopher A. Beaudoin Martin Bartas Adriana Volná Petr Pečinka Tom L. Blundell |
| author_facet | Christopher A. Beaudoin Martin Bartas Adriana Volná Petr Pečinka Tom L. Blundell |
| author_sort | Christopher A. Beaudoin |
| collection | DOAJ |
| description | Due to the fast global spreading of the Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2), prevention and treatment options are direly needed in order to control infection-related morbidity, mortality, and economic losses. Although drug and inactivated and attenuated virus vaccine development can require significant amounts of time and resources, DNA and RNA vaccines offer a quick, simple, and cheap treatment alternative, even when produced on a large scale. The spike protein, which has been shown as the most antigenic SARS-CoV-2 protein, has been widely selected as the target of choice for DNA/RNA vaccines. Vaccination campaigns have reported high vaccination rates and protection, but numerous unintended effects, ranging from muscle pain to death, have led to concerns about the safety of RNA/DNA vaccines. In parallel to these studies, several open reading frames (ORFs) have been found to be overlapping SARS-CoV-2 accessory genes, two of which, ORF2b and ORF-Sh, overlap the spike protein sequence. Thus, the presence of these, and potentially other ORFs on SARS-CoV-2 DNA/RNA vaccines, could lead to the translation of undesired proteins during vaccination. Herein, we discuss the translation of overlapping genes in connection with DNA/RNA vaccines. Two mRNA vaccine spike protein sequences, which have been made publicly-available, were compared to the wild-type sequence in order to uncover possible differences in putative overlapping ORFs. Notably, the Moderna mRNA-1273 vaccine sequence is predicted to contain no frameshifted ORFs on the positive sense strand, which highlights the utility of codon optimization in DNA/RNA vaccine design to remove undesired overlapping ORFs. Since little information is available on ORF2b or ORF-Sh, we use structural bioinformatics techniques to investigate the structure-function relationship of these proteins. The presence of putative ORFs on DNA/RNA vaccine candidates implies that overlapping genes may contribute to the translation of smaller peptides, potentially leading to unintended clinical outcomes, and that the protein-coding potential of DNA/RNA vaccines should be rigorously examined prior to administration. |
| first_indexed | 2024-12-24T01:48:23Z |
| format | Article |
| id | doaj.art-04fce1eb78dc496c94f60c9e8e4696f1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-24T01:48:23Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-04fce1eb78dc496c94f60c9e8e4696f12022-12-21T17:21:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-02-011310.3389/fimmu.2022.801915801915Are There Hidden Genes in DNA/RNA Vaccines?Christopher A. Beaudoin0Martin Bartas1Adriana Volná2Petr Pečinka3Tom L. Blundell4Department of Biochemistry, Sanger Building, University of Cambridge, Cambridge, United KingdomDepartment of Biology and Ecology, University of Ostrava, Ostrava, CzechiaDepartment of Physics, University of Ostrava, Ostrava, CzechiaDepartment of Biology and Ecology, University of Ostrava, Ostrava, CzechiaDepartment of Biochemistry, Sanger Building, University of Cambridge, Cambridge, United KingdomDue to the fast global spreading of the Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2), prevention and treatment options are direly needed in order to control infection-related morbidity, mortality, and economic losses. Although drug and inactivated and attenuated virus vaccine development can require significant amounts of time and resources, DNA and RNA vaccines offer a quick, simple, and cheap treatment alternative, even when produced on a large scale. The spike protein, which has been shown as the most antigenic SARS-CoV-2 protein, has been widely selected as the target of choice for DNA/RNA vaccines. Vaccination campaigns have reported high vaccination rates and protection, but numerous unintended effects, ranging from muscle pain to death, have led to concerns about the safety of RNA/DNA vaccines. In parallel to these studies, several open reading frames (ORFs) have been found to be overlapping SARS-CoV-2 accessory genes, two of which, ORF2b and ORF-Sh, overlap the spike protein sequence. Thus, the presence of these, and potentially other ORFs on SARS-CoV-2 DNA/RNA vaccines, could lead to the translation of undesired proteins during vaccination. Herein, we discuss the translation of overlapping genes in connection with DNA/RNA vaccines. Two mRNA vaccine spike protein sequences, which have been made publicly-available, were compared to the wild-type sequence in order to uncover possible differences in putative overlapping ORFs. Notably, the Moderna mRNA-1273 vaccine sequence is predicted to contain no frameshifted ORFs on the positive sense strand, which highlights the utility of codon optimization in DNA/RNA vaccine design to remove undesired overlapping ORFs. Since little information is available on ORF2b or ORF-Sh, we use structural bioinformatics techniques to investigate the structure-function relationship of these proteins. The presence of putative ORFs on DNA/RNA vaccine candidates implies that overlapping genes may contribute to the translation of smaller peptides, potentially leading to unintended clinical outcomes, and that the protein-coding potential of DNA/RNA vaccines should be rigorously examined prior to administration.https://www.frontiersin.org/articles/10.3389/fimmu.2022.801915/fullSARS-CoV-2spike proteinDNA vaccineRNA vaccineORF2bORF-Sh |
| spellingShingle | Christopher A. Beaudoin Martin Bartas Adriana Volná Petr Pečinka Tom L. Blundell Are There Hidden Genes in DNA/RNA Vaccines? Frontiers in Immunology SARS-CoV-2 spike protein DNA vaccine RNA vaccine ORF2b ORF-Sh |
| title | Are There Hidden Genes in DNA/RNA Vaccines? |
| title_full | Are There Hidden Genes in DNA/RNA Vaccines? |
| title_fullStr | Are There Hidden Genes in DNA/RNA Vaccines? |
| title_full_unstemmed | Are There Hidden Genes in DNA/RNA Vaccines? |
| title_short | Are There Hidden Genes in DNA/RNA Vaccines? |
| title_sort | are there hidden genes in dna rna vaccines |
| topic | SARS-CoV-2 spike protein DNA vaccine RNA vaccine ORF2b ORF-Sh |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.801915/full |
| work_keys_str_mv | AT christopherabeaudoin aretherehiddengenesindnarnavaccines AT martinbartas aretherehiddengenesindnarnavaccines AT adrianavolna aretherehiddengenesindnarnavaccines AT petrpecinka aretherehiddengenesindnarnavaccines AT tomlblundell aretherehiddengenesindnarnavaccines |