Inhibition of influenza M2-induced cell death alleviates its negative contribution to vaccination efficiency
The effectiveness of recombinant vaccines encoding full-length M2 protein of influenza virus or its ectodomain (M2e) have previously been tested in a number of models with varying degrees of success. Recently, we reported a strong cytotoxic effect exhibited by M2 on mammalian cells in vitro. Here we...
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| creator | Ilyinskii, Petr O Gambaryan, Alexandra S Meriin, Anatoli B Gabai, Vladimir Kartashov, Alex Thoidis, Galini Shneider, Alexander M |
| description | The effectiveness of recombinant vaccines encoding full-length M2 protein of influenza virus or its ectodomain (M2e) have previously been tested in a number of models with varying degrees of success. Recently, we reported a strong cytotoxic effect exhibited by M2 on mammalian cells in vitro. Here we demonstrated a decrease in protection when M2 was added to a DNA vaccination regimen that included influenza NP. Furthermore, we have constructed several fusion proteins of conserved genes of influenza virus and tested their expression in vitro and protective potential in vivo. The four-partite NP-M1-M2-NS1 fusion antigen that has M2 sequence engineered in the middle part of the composite protein was shown to not be cytotoxic in vitro. A three-partite fusion protein (consisting of NP, M1 and NS1) was expressed much more efficiently than the four-partite protein. Both of these constructs provided statistically significant protection upon DNA vaccination, with construct NP-M1-M2-NS1 being the most effective. We conclude that incorporation of M2 into a vaccination regimen may be beneficial only when its apparent cytotoxicity-linked negative effects are neutralized. The possible significance of this data for influenza vaccination regimens and preparations is discussed. |
| doi_str_mv | 10.1371/journal.pone.0001417 |
| format | Article |
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Recently, we reported a strong cytotoxic effect exhibited by M2 on mammalian cells in vitro. Here we demonstrated a decrease in protection when M2 was added to a DNA vaccination regimen that included influenza NP. Furthermore, we have constructed several fusion proteins of conserved genes of influenza virus and tested their expression in vitro and protective potential in vivo. The four-partite NP-M1-M2-NS1 fusion antigen that has M2 sequence engineered in the middle part of the composite protein was shown to not be cytotoxic in vitro. A three-partite fusion protein (consisting of NP, M1 and NS1) was expressed much more efficiently than the four-partite protein. Both of these constructs provided statistically significant protection upon DNA vaccination, with construct NP-M1-M2-NS1 being the most effective. We conclude that incorporation of M2 into a vaccination regimen may be beneficial only when its apparent cytotoxicity-linked negative effects are neutralized. 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Recently, we reported a strong cytotoxic effect exhibited by M2 on mammalian cells in vitro. Here we demonstrated a decrease in protection when M2 was added to a DNA vaccination regimen that included influenza NP. Furthermore, we have constructed several fusion proteins of conserved genes of influenza virus and tested their expression in vitro and protective potential in vivo. The four-partite NP-M1-M2-NS1 fusion antigen that has M2 sequence engineered in the middle part of the composite protein was shown to not be cytotoxic in vitro. A three-partite fusion protein (consisting of NP, M1 and NS1) was expressed much more efficiently than the four-partite protein. Both of these constructs provided statistically significant protection upon DNA vaccination, with construct NP-M1-M2-NS1 being the most effective. We conclude that incorporation of M2 into a vaccination regimen may be beneficial only when its apparent cytotoxicity-linked negative effects are neutralized. The possible significance of this data for influenza vaccination regimens and preparations is discussed.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>18197240</pmid><doi>10.1371/journal.pone.0001417</doi><tpages>e1417</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigens Apoptosis Biochemistry Biocompatibility Blotting, Western Cell cycle Cell death Cell Death - physiology Cell Line Cells (Biology) Cytotoxicity Deoxyribonucleic acid DNA DNA vaccines Efficiency Fusion protein Gene expression Hogs Influenza Influenza vaccines Influenza Vaccines - immunology Influenza virus Influenza viruses Mammalian cells Orthomyxoviridae - physiology Orthomyxoviridae Infections - immunology Orthomyxoviridae Infections - pathology Plasmids Proteins Statistical analysis Toxicity Vaccination Vaccines Virology Virology/Vaccines Viruses |
| title | Inhibition of influenza M2-induced cell death alleviates its negative contribution to vaccination efficiency |
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