Inactivation and Removal of Chikungunya Virus and Mayaro Virus from Plasma-derived Medicinal Products

Abstract

Background: Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are closely related members of the Semliki Forest complex within the genus alphavirus and are transmitted by arthropods, causing acute febrile illness in humans. CHIKV has spread to almost all continents, whereas autochthonous MAYV infections have been reported in South America and in the Caribbean. Nevertheless, there was concern about potential spread of MAYV to other regions similar to CHIKV in the past. The risk for transmission of emerging viruses by blood transfusion and the safety of plasma-derived medicinal products (PDMPs) are constant concerns. The manufacturing processes of PDMPs include procedures to inactivate/remove viruses. Methods: In this study, we investigated the reduction of MAYV and CHIKV by heat inactivation in various matrices, solvent/detergent treatment and nanofiltration. Results: Unexpectedly, MAYV was significantly more resistant to heat and solvent/detergent treatment compared to CHIKV. However, being similar in size, both MAYV and CHIKV were removed below the detection limit by 35 nm virus filters. Conclusions: The inactivation profiles of different alphavirus members vary considerably, even within the Semliki Forest Complex. However, robust dedicated viral inactivation/removal procedures commonly used in the plasma product industry are effective in inactivating or removing MAYV and CHIKV.

Energy Requirements for Loss of Viral Infectivity

“…Viral inactivation occurs when the proteins on the surface of the particle change shape, and as a result, lose their ability to function properly, removing their ability to infect cells (Keller et al 2018;Snyder et al 2019;Whitehurst et al 2007). Understanding viral inactivation is important for determining transmission of viruses (Yue et al 2019;Pinon and Vialette 2018;Predmore et al 2015), but also plays a role in vaccine development (Dumard et al 2017;Silva et al 2015).…”

“…Understanding viral inactivation is important for determining transmission of viruses (Yue et al. 2019 ; Pinon and Vialette 2018 ; Predmore et al. 2015 ), but also plays a role in vaccine development (Dumard et al.…”

Aggregate Removal Nanofiltration of Human Serum Albumin Solution Using Nanocellulose-Based Filter Paper

“…The time of pasteurization is critical for efficient inactivation of virus particles, e.g., 4 h pasteurization may not be sufficient to inactivate hepatitis B viruses as opposed to a 10 h treatment [12]. While the method has been widely accepted in manufacturing of HSA in industry, the emergence of new viruses, e.g., Zika virus and Chikungunya virus, stipulates constant revalidation of the process [13][14][15][16][17]. Pasteurization of HSA (60 • C, 10 h) was shown to reduce the infectivity of most known human viruses including human parvovirus B19, hepatitis A virus, human immunodeficiency virus and West Nile virus [18][19][20][21], but it may be ineffective against animal parvoviruses, e.g., canine parvovirus (CPV) and minute virus of mice (MVM) [21].…”

Chikungunya Virus and (Re-) Emerging Alphaviruses

“…Thus, phylogenetic and epidemiological studies, clinical diagnostics, vaccine/antiviral drug development, basic research including virus-vector interaction, transmission, viral immunity, and pathogenesis are still necessary for alphaviral disease prevention. In this special issue of “Chikungunya Virus and (Re-) Emerging Alphaviruses”, we solicit 10 research articles and six review articles covering the development of vaccines and antivirals [1,2,3,4], pathogenesis/immunity [5,6,7,8], viral evolution [9], development of research/diagnostic tools [10,11], vector-virus interaction [12,13], as well as mechanisms of transmission [14].…”

“…As alphaviruses are blood-borne and could be transmitted by blood transfusion, they pose severe safety concerns for plasma-derived medicinal products (PDMPs) in the epidemic countries. Yue et al have described methods to inactivate/remove the CHIKV and the Mayaro virus (MAYV) from PDMPs [4]. These methods could also be a useful guide for the preparation of inactivated virus vaccines.…”