New chemical method of viral inactivation for vaccine development based on membrane fusion inhibition.
Membrane fusion is an essential step in the entry of enveloped viruses into their host cells. This process is triggered by conformational changes in viral surface glycoproteins. We have demonstrated previously that modification of vesicular stomatitis virus (VSV) with diethylpyrocarbonate (DEPC) abolished the conformational changes on VSV glycoprotein and the fusion reaction induced by the virus. Moreover, we observed that viral treatment with DEPC inactivates the virus, preserving the conformational integrity of its surface proteins. In the present work, we evaluated the potential use of DEPC as a viral inactivating chemical agent for the development of useful vaccines. Pathogenicity and viral replication in Balb/c mice were abolished by viral treatment with 0.5mM DEPC. In addition, antibodies elicited in mice after intraperitoneal immunization with DEPC-inactivated VSV mixed with adjuvants were able to recognize and neutralize the native virus and efficiently protected animals against the challenge with lethal doses of VSV. These results together suggest that viral inactivation with DEPC seems to be a suitable method for the development of safe vaccines.
Stauffer
Fausto
F
Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-590, Brazil.
De Miranda
Joari
J
Schechter
Marcos C
MC
Queiroz
Fernando A
FA
Santos
Nathalia O
NO
Alves
Ada M B
AM
Da Poian
Andrea T
AT
D000818:Animals; D006224:Cricetinae; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology*; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011487:Protein Conformation / Q000187:drug effects; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000517:prevention & control; D015164:Vaccines, Inactivated / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000472:pathogenicity / Q000502:physiology*; D014760:Viral Fusion Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D038301:Virus Inactivation / Q000187:drug effects*; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
D015164:Vaccines, Inactivated; D014760:Viral Fusion Proteins; D014765:Viral Vaccines; D004047:Diethyl Pyrocarbonate