Visible 405 nm Violet-Blue Light Successfully Inactivates HIV-1 in Human Plasma

Abstract

Despite significant advances in ensuring the safety of the blood supply, there is continued risk of transfusion transmitted infections (TTIs) from newly emerging or re-emerging infections. Globally, several pathogen reduction technologies (PRTs) for blood safety have been in development as an alternative to traditional treatment methods. Despite broad spectrum antimicrobial efficacy, some of the approved ultraviolet (UV) light-based PRTs, understandably due to UV light-associated toxicities, fall short in preserving the full functional spectrum of the treated blood components. As a safer alternative to the UV-based microbicidal technologies, investigations into the use of violet-blue light in the region of 405 nm have been on the rise as these wavelengths do not impair the treated product at doses that demonstrate microbicidal activity. Recently, we have demonstrated that a 405 nm violet-blue light dose of 270 J/cm2 was sufficient for reducing bacteria and the parasite in plasma and platelets suspended in plasma while preserving the quality of the treated blood product stored for transfusion. Drawn from the previous experience, here we evaluated the virucidal potential of 405 nm violet-blue light dose of 270 J/cm2 on an important blood-borne enveloped virus, the human immunodeficiency virus 1 (HIV-1), in human plasma. Both test plasma (HIV-1 spiked and treated with various doses of 405 nm light) and control plasma (HIV-1 spiked, but not treated with the light) samples were cultured with HIV-1 permissive H9 cell line for up to 21 days to estimate the viral titers. Quantitative HIV-1 p24 antigen (HIV-1 p24) levels reflective of HIV-1 titers were measured for each light dose to assess virus infectivity. Our results demonstrate that a 405 nm light dose of 270 J/cm2 is also capable of 4–5 log HIV-1 reduction in plasma under the conditions tested. Overall, this study provides the first proof-of-concept that 405 nm violet-blue light successfully inactivates HIV-1 present in human plasma, thereby demonstrating its potential towards being an effective PRT for this blood component safety.

The Preclinical Validation of 405 nm Light Parasiticidal Efficacy on Leishmania donovani in Ex Vivo Platelets in a Rag2−/− Mouse Model

“…The 405 nm light treatment of platelets was performed in a closed system (US Patent Application no. 62/236, 706, 2015) as previously reported (7,3,8). Briefly, the system contained a light source consisting of narrowband 405 nm LED arrays (FWHM ~20 nm; LED Engin, San Jose, CA, USA), with appropriate thermal management, and powered by LED drivers (Mean Well, Xinbei, Taiwan) and a shaker platform to have 60 rpm and 22 • C in order to provide the continuous agitation of the sample while maintaining consistent treatment conditions.…”

“…These technologies require the addition of chelators, and sample exposure to UV light has been reported to reduce the in vitro quality of platelets [ 15 ], which calls for alternative methods that are gentler to the platelets. We have previously shown that 405 nm light is a potent pathogen inactivator for a number of bacteria, HIV-1, and the Trypanosoma cruzi parasite, while it is gentle on treated plasma and platelets in human plasma and on platelets stored for transfusion [ 3 , 4 , 5 , 6 , 7 , 8 ]. Platelets treated with 405 nm light behaved similar to the light-untreated platelets in terms of in vitro parameters such as pH, lactate release, activation/aggregation responses to collagen, and the in vivo response of survival and recovery in an immunodeficient SCID mouse model [ 3 , 7 ].…”

“…The microbicidal efficacy of 405 nm light has been shown for various pathogens so far. Ragupathy et al have shown that 405 nm light can inactivate HIV-1 in human plasma [ 8 ]. Similarly, Jankowska et al noted the ability of 405 nm light to inactivate the Trypanosoma cruzi parasite present in human platelets [ 3 ].…”

“…Especially since platelets are stored at room temperature, they are vulnerable to microbial contamination and subsequent growth; it is important to evaluate the microbicidal effect of 405 nm light in platelets stored in plasma. We have shown that 405 nm light is a potent pathogen inactivator for a number of bacteria, HIV-1, and a parasite Trypanosoma cruzi , while gentle on the treated human plasma and platelets stored for transfusion [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ].…”

Human platelet concentrates treated with microbicidal 405 nm light retain hemostasis activity

“…This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4715023 P r e p r i n t n o t p e e r r e v i e w e d Human platelet concentrates treated with microbicidal 405 nm light retain hemostasis activity several bacteria, HIV-1, and parasites in plasma alone or in platelets suspended in plasma [8,9]. Further, we have shown that microbicidal 405 nm light does not affect the recovery and survival of the lighttreated platelets in a SCID mouse model [10], demonstrating the safety of the treatment for ex vivo platelets.…”