Characterization of humoral and cellular immune features of gamma-irradiated influenza vaccine

Chen, Fengjia; Seo, Ho Seong; Ji, Hyun Jung; Yang, Eun Ae; Choi, Jung Ah; Yang, Jae Seung; Song, Manki; Han, Seung Hyun; Lim, Sangyong; Lim, Jae Hyang; Ahn, Kyu Jeung

doi:10.1080/21645515.2020.1780091

Cited by 12 publications

(12 citation statements)

References 62 publications

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“…It is well known that the use of formaldehyde, in the form of the aqueous solution formalin, for vaccine production can cause a variety of immunological issues because it can alter the structure of antigenic epitopes (43,44) and diminish the production of pathogen-specific and functional antibodies. We reported that formalin inactivation could decrease the humoral immune response by impairing the activity of influenza surface antigens hemagglutinin (HA) and neuraminidase (NA) (45). In this study, we also showed that formalin treatment of SG (f-SG) dramatically increased the carbonylation of SG proteins compared to untreated cells or r-SG.…”

Section: Discussionmentioning

confidence: 66%

Radiation-Inactivated S. gallinarum Vaccine Provides a High Protective Immune Response by Activating Both Humoral and Cellular Immunity

Byun

Chen

et al. 2021

Front. Immunol.

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Salmonella enterica subsp. enterica serovar Gallinarum (SG) is a common pathogen in chickens, and causes an acute systemic disease that leads to high mortality. The live attenuated vaccine 9R is able to successfully protect chickens older than six weeks by activating a robust cell-mediated immune response, but its safety and efficacy in young chickens remains controversial. An inactivated SG vaccine is being used as an alternative, but because of its low cellular immune response, it cannot be used as a replacement for live attenuated 9R vaccine. In this study, we employed gamma irradiation instead of formalin as an inactivation method to increase the efficacy of the inactivated SG vaccine. Humoral, cellular, and protective immune responses were compared in both mouse and chicken models. The radiation-inactivated SG vaccine (r-SG) induced production of significantly higher levels of IgG2b and IgG3 antibodies than the formalin-inactivated vaccine (f-SG), and provided a homogeneous functional antibody response against group D, but not group B Salmonella. Moreover, we found that r-SG vaccination could provide a higher protective immune response than f-SG by inducing higher Th17 activation. These results indicate that r-SG can provide a protective immune response similar to the live attenuated 9R vaccine by activating a higher humoral immunity and a lower, but still protective, cellular immune response. Therefore, we expect that the radiation inactivation method might substitute for the 9R vaccine with little or no side effects in chickens younger than six weeks.

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Section: Discussionmentioning

confidence: 66%

Radiation-Inactivated S. gallinarum Vaccine Provides a High Protective Immune Response by Activating Both Humoral and Cellular Immunity

Byun

Chen

et al. 2021

Front. Immunol.

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“…The inoculated eggs were incubated at 37°C and observed every 24 h to detect mortality for 7 days. Allantoic fluids harvested from the eggs were tested by the HA assay to detect viral replication, according to standard procedures ( 24 ). Allantoic fluids showing the absence of hemagglutinating activity were considered as negative for virus replication.…”

Section: Methodsmentioning

confidence: 99%

Protective Efficacy of H9N2 Avian Influenza Vaccines Inactivated by Ionizing Radiation Methods Administered by the Parenteral or Mucosal Routes

et al. 2022

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H9N2 viruses have become, over the last 20 years, one of the most diffused poultry pathogens and have reached a level of endemicity in several countries. Attempts to control the spread and reduce the circulation of H9N2 have relied mainly on vaccination in endemic countries. However, the high level of adaptation to poultry, testified by low minimum infectious doses, replication to high titers, and high transmissibility, has severely hampered the results of vaccination campaigns. Commercially available vaccines have demonstrated high efficacy in protecting against clinical disease, but variable results have also been observed in reducing the level of replication and viral shedding in domestic poultry species. Antigenic drift and increased chances of zoonotic infections are the results of incomplete protection offered by the currently available vaccines, of which the vast majority are based on formalin-inactivated whole virus antigens. In our work, we evaluated experimental vaccines based on an H9N2 virus, inactivated by irradiation treatment, in reducing viral shedding upon different challenge doses and compared their efficacy with formalin-inactivated vaccines. Moreover, we evaluated mucosal delivery of inactivated antigens as an alternative route to subcutaneous and intramuscular vaccination. The results showed complete protection and prevention of replication in subcutaneously vaccinated Specific Pathogen Free White Leghorn chickens at low-to-intermediate challenge doses but a limited reduction of shedding at a high challenge dose. Mucosally vaccinated chickens showed a more variable response to experimental infection at all tested challenge doses and the main effect of vaccination attained the reduction of infected birds in the early phase of infection. Concerning mucosal vaccination, the irradiated vaccine was the only one affording complete protection from infection at the lowest challenge dose. Vaccine formulations based on H9N2 inactivated by irradiation demonstrated a potential for better performances than vaccines based on the formalin-inactivated antigen in terms of reduction of shedding and prevention of infection.

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“…It has been thought that modern subunit vaccines would provide a solution, since they can be developed more easily (15). However, recent successful development of irradiated vaccines for human malaria (16) and influenza (17,18) have not only demonstrated the feasibility and practicality of this technique, but also the efficacy of such vaccination approaches, prompting research in applying the method to other viruses (19,20). Yet, it is known that high-dose c-ray exposure can damage epitopes necessary to elicit the immune response (21).…”

Section: Introductionmentioning

confidence: 99%

Monte Carlo Simulation of SARS-CoV-2 Radiation-Induced Inactivation for Vaccine Development

et al. 2021

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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 (c) 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 c 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.

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Characterization of humoral and cellular immune features of gamma-irradiated influenza vaccine

Cited by 12 publications

References 62 publications

Radiation-Inactivated S. gallinarum Vaccine Provides a High Protective Immune Response by Activating Both Humoral and Cellular Immunity

Radiation-Inactivated S. gallinarum Vaccine Provides a High Protective Immune Response by Activating Both Humoral and Cellular Immunity

Protective Efficacy of H9N2 Avian Influenza Vaccines Inactivated by Ionizing Radiation Methods Administered by the Parenteral or Mucosal Routes

Monte Carlo Simulation of SARS-CoV-2 Radiation-Induced Inactivation for Vaccine Development

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