Abstract
Immunization with an inactivated virus is one of the strategies currently being tested towards developing a SARS-CoV-2 vaccine. One of the methods used to inactivate viruses is exposure to high doses of ionizing radiation to damage their nucleic acids. While gamma (γ) rays effectively induce lesions in the RNA, envelope proteins are also highly damaged in the process. This in turn may alter their antigenic properties, affecting their capacity to induce an adaptive immune response able to confer effective protection. Here, we modeled the effect of sparsely and densely ionizing radiation on SARS-CoV-2 using the Monte Carlo toolkit Geant4-DNA. With a realistic 3D target virus model, we calculated the expected number of lesions in the spike and membrane proteins, as well as in the viral RNA. Our findings showed that γ rays produced significant spike protein damage, but densely ionizing charged particles induced less membrane damage for the same level of RNA lesions, because a single ion traversal through the nuclear envelope was sufficient to inactivate the virus. We propose that accelerated charged particles produce inactivated viruses with little structural damage to envelope proteins, thereby representing a new and effective tool for developing vaccines against SARS-CoV-2 and other enveloped viruses.
Highlights
The threat from the new SARS-CoV-2 is omnipresent in all regions of the world [1]
MRNA vaccines are emerging as very attractive alternatives, due to their ease of manufacture and potent immune response [11], but their long-term effectiveness and safety remains to be elucidated in comparison to the wellestablished inactivated virus standard
Simulation of radiation damage in SARS-CoV-2 is interesting for many reasons
Summary
The threat from the new SARS-CoV-2 is omnipresent in all regions of the world [1]. Several companies and research groups are reporting promising results in the development of vaccines [2,3,4]. Some of the SARS-CoV vaccines developed to date follow the traditional approach based on inactivated or live attenuated viruses [5,6,7,8]. CoV-2 virus is sensitive to the standard inactivation methods used for producing vaccines against other viral diseases [9]. Live attenuated virus-based vaccines generally induce potent cellular immune response, antibody production is often less efficient, and the use of attenuated viruses is often not indicated in individuals who are immunosuppressed as a result of disease or therapeutic interventions. MRNA vaccines are emerging as very attractive alternatives, due to their ease of manufacture and potent immune response [11], but their long-term effectiveness and safety remains to be elucidated in comparison to the wellestablished inactivated virus standard
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