Low-Energy Electron Irradiation (LEEI) for the Generation of Inactivated Bacterial Vaccines

Fertey, Jasmin; Standfest, Bastian; Beckmann, Jana; Thoma, Martin; Grünwald, Thomas; Ulbert, Sebastian

doi:10.1007/978-1-0716-1900-1_7

Cited by 3 publications

(3 citation statements)

References 16 publications

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“…LEEI was used as a non-toxic and non-probe-harming inactivation method with improved safety compared to chemical inactivation or other radiation methods. It has been used successfully for the generation of several viral, bacterial, and parasitic vaccine candidates (19)(20)(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Mucosal immunization with a low-energy electron inactivated respiratory syncytial virus vaccine protects mice without Th2 immune bias

Eberlein,

Rosencrantz,

Finkensieper

et al. 2024

Front. Immunol.

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The respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections associated with numerous hospitalizations. Recently, intramuscular (i.m.) vaccines against RSV have been approved for elderly and pregnant women. Noninvasive mucosal vaccination, e.g., by inhalation, offers an alternative against respiratory pathogens like RSV. Effective mucosal vaccines induce local immune responses, potentially resulting in the efficient and fast elimination of respiratory viruses after natural infection. To investigate this immune response to an RSV challenge, low-energy electron inactivated RSV (LEEI-RSV) was formulated with phosphatidylcholine-liposomes (PC-LEEI-RSV) or 1,2-dioleoyl-3-trimethylammonium-propane and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DD-LEEI-RSV) for vaccination of mice intranasally. As controls, LEEI-RSV and formalin-inactivated-RSV (FI-RSV) were used via i.m. vaccination. The RSV-specific immunogenicity of the different vaccines and their protective efficacy were analyzed. RSV-specific IgA antibodies and a statistically significant reduction in viral load upon challenge were detected in mucosal DD-LEEI-RSV-vaccinated animals. Alhydrogel-adjuvanted LEEI-RSV i.m. showed a Th2-bias with enhanced IgE, eosinophils, and lung histopathology comparable to FI-RSV. These effects were absent when applying the mucosal vaccines highlighting the potential of DD-LEEI-RSV as an RSV vaccine candidate and the improved performance of this mucosal vaccine candidate.

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Section: Introductionmentioning

confidence: 99%

Mucosal immunization with a low-energy electron inactivated respiratory syncytial virus vaccine protects mice without Th2 immune bias

Eberlein,

Rosencrantz,

Finkensieper

et al. 2024

Front. Immunol.

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“…Virus inactivation approaches, especially those using physical methods, are safe and have low production costs [ 38 , 39 , 40 ]. We have shown previously that low-energy electron irradiation (LEEI) is a safe, non-toxic, and non-probe harming inactivation method [ 41 , 42 , 43 , 44 , 45 , 46 ]. The advantage over other irradiation methods is that the emission of secondary photon radiation is minimal, reducing the need for extensive shielding and making LEEI-technologies applicable in standard laboratories [ 43 , 47 ].…”

Section: Introductionmentioning

confidence: 99%

“…The advantage over other irradiation methods is that the emission of secondary photon radiation is minimal, reducing the need for extensive shielding and making LEEI-technologies applicable in standard laboratories [ 43 , 47 ]. Since the penetration depth of low-energy electrons is highly limited [ 48 , 49 ], we have developed automated processes that generate thin liquid films, enabling the efficient LEEI of pathogens in suspension up to multi-liter scales [ 41 , 42 , 43 , 46 ]. LEEI has advantages over other radiation types such as ultraviolet (UV) light.…”

Section: Introductionmentioning

confidence: 99%

Mucosal Application of a Low-Energy Electron Inactivated Respiratory Syncytial Virus Vaccine Shows Protective Efficacy in an Animal Model

Eberlein,

Ahrends,

Bayer

et al. 2023

Viruses

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Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in the elderly and in children, associated with pediatric hospitalizations. Recently, first vaccines have been approved for people over 60 years of age applied by intramuscular injection. However, a vaccination route via mucosal application holds great potential in the protection against respiratory pathogens like RSV. Mucosal vaccines induce local immune responses, resulting in a fast and efficient elimination of respiratory viruses after natural infection. Therefore, a low-energy electron irradiated RSV (LEEI-RSV) formulated with phosphatidylcholine-liposomes (PC-LEEI-RSV) was tested ex vivo in precision cut lung slices (PCLSs) for adverse effects. The immunogenicity and protective efficacy in vivo were analyzed in an RSV challenge model after intranasal vaccination using a homologous prime-boost immunization regimen. No side effects of PC-LEEI-RSV in PCLS and an efficient antibody induction in vivo could be observed. In contrast to unformulated LEEI-RSV, the mucosal vaccination of mice with PC formulated LEEI-RSV showed a statistically significant reduction in viral load after challenge. These results are a proof-of-principle for the use of LEEI-inactivated viruses formulated with liposomes to be administered intranasally to induce a mucosal immunity that could also be adapted for other respiratory viruses.

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Viral inactivation by light

Sadraeian

Zhang

Aavani

et al. 2022

eLight

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Nowadays, viral infections are one of the greatest challenges for medical sciences and human society. While antiviral compounds and chemical inactivation remain inadequate, physical approaches based on irradiation provide new potentials for prevention and treatment of viral infections, without the risk of drug resistance and other unwanted side effects. Light across the electromagnetic spectrum can inactivate the virions using ionizing and non-ionizing radiations. This review highlights the anti-viral utility of radiant methods from the aspects of ionizing radiation, including high energy ultraviolet, gamma ray, X-ray, and neutron, and non-ionizing photo-inactivation, including lasers and blue light.

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Low-Energy Electron Irradiation (LEEI) for the Generation of Inactivated Bacterial Vaccines

Cited by 3 publications

References 16 publications

Mucosal immunization with a low-energy electron inactivated respiratory syncytial virus vaccine protects mice without Th2 immune bias

Mucosal immunization with a low-energy electron inactivated respiratory syncytial virus vaccine protects mice without Th2 immune bias

Mucosal Application of a Low-Energy Electron Inactivated Respiratory Syncytial Virus Vaccine Shows Protective Efficacy in an Animal Model

Viral inactivation by light

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