Enhanced Immunogenicity of a Whole-Inactivated Influenza A Virus Vaccine Using Optimised Irradiation Conditions

Singleton, Eve V.; Gates, Chloe J.; David, Shannon C.; Hirst, Timothy R.; Davies, Justin; Alsharifi, Mohammed

doi:10.3389/fimmu.2021.761632

Cited by 4 publications

(7 citation statements)

References 35 publications

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“…When administered SC, no significant differences were recorded in terms of immunogenicity between the two vaccines. However, HI titers were higher than previously reported for similar antigen concentrations (50,55), possibly as the result of either optimal vaccine preparation and administration (e.g., type of adjuvant) or due to the presence of trehalose in vaccine batches, whose activity on the modulation of host immunity is well-documented (56). Excellent results of ISA71VG as an adjuvant for AIV vaccine preparation have also been previously demonstrated in a study performed by Lone and colleagues (57) who compared 10 different commercial and experimental adjuvants for use in chickens, identifying ISA71 VG to perform best in terms of clinical protection and reduction of viral shedding in experimentally infected SPF chickens.…”

Section: Discussioncontrasting

confidence: 80%

“…In our work, to minimize the deleterious effects of γ-irradiation, we also used trehalose as a radio-protectant to preserve the antigenic epitopes during the irradiation process. Trehalose is a well-known cryo-protectant that stabilizes proteins and has been shown to protect DNA during radiation ( 50 ). Indeed, trehalose has been used widely in viral vaccine formulations to achieve stabilization of the antigens ( 51 , 52 ).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussioncontrasting

confidence: 80%

Section: Discussionmentioning

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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“…The discrepancy is likely to be based on different irradiation conditions, such as media or temperature. It has been shown that sensitivity to ionizing radiation increases at higher temperatures (31). Hruskováand this study used samples at room temperature or 4°C, respectively.…”

Section: Discussionmentioning

confidence: 97%

Low-Energy Electron Irradiation of Tick-Borne Encephalitis Virus Provides a Protective Inactivated Vaccine

et al. 2022

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Tick-borne encephalitis virus (TBEV) is a zoonotic flavivirus which is endemic in many European and Asian countries. Humans can get infected with TBEV usually via ticks, and possible symptoms of the infection range from fever to severe neurological complications such as encephalitis. Vaccines to protect against TBEV-induced disease are widely used and most of them consist of whole viruses, which are inactivated by formaldehyde. Although this production process is well established, it has several drawbacks, including the usage of hazardous chemicals, the long inactivation times required and the potential modification of antigens by formaldehyde. As an alternative to chemical treatment, low-energy electron irradiation (LEEI) is known to efficiently inactivate pathogens by predominantly damaging nucleic acids. In contrast to other methods of ionizing radiation, LEEI does not require substantial shielding constructions and can be used in standard laboratories. Here, we have analyzed the potential of LEEI to generate a TBEV vaccine and immunized mice with three doses of irradiated or chemically inactivated TBEV. LEEI-inactivated TBEV induced binding antibodies of higher titer compared to the formaldehyde-inactivated virus. This was also observed for the avidity of the antibodies measured after the second dose. After viral challenge, the mice immunized with LEEI- or formaldehyde-inactivated TBEV were completely protected from disease and had no detectable virus in the central nervous system. Taken together, the results indicate that LEEI could be an alternative to chemical inactivation for the production of a TBEV vaccine.

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“…Our results were consistent with previous studies, 28 in which low antibody titers after the first dose with a moderate rise of antibody concentrations after the second dose were observed in persons who received inactivated vaccines. To enhance the immunogenicity of inactivated vaccines, increased vaccine dose, adjuvant types, and downstream processes for viral inactivation can be optimized, such as irradiation conditions, concentration, and purification of vaccines 29–31 …”

Section: Discussionmentioning

confidence: 99%

“…To enhance the immunogenicity of inactivated vaccines, increased vaccine dose, adjuvant types, and downstream processes for viral inactivation can be optimized, such as irradiation conditions, concentration, and purification of vaccines. [29][30][31] Clinical factors were also verified to influence antibody levels in with severe diseases has been reported to be associated with SARS-CoV-2 N protein. 41 It may be correlated with the stronger immune response in the infected individuals.…”

Section: Different Expression Of Cytokines Between Previously Infecte...mentioning

confidence: 99%

Distinct immune responses in the early phase to natural SARS‐CoV‐2 infection or vaccination

Peng¹,

Deng²,

Li³

et al. 2022

Journal of Medical Virology

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Immune responses elicited by viral infection or vaccination play key roles in the viral elimination and the prevention of reinfection, as well as the protection of healthy persons. As one of the most widely used Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there have been increasing concerns about the necessity of additional doses of inactivated vaccines, due to the waning immune response several months after vaccination. To further optimize inactivated SARS-CoV-2 vaccines, we compared immune responses to SARS-CoV-2 elicited by natural infection and immunization with inactivated vaccines in the early phase. We observed the lower antibody levels against SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in the early phase of postvaccination with a slow increase, compared to the acute phase of SARS-CoV-2 natural infection. Specifically, IgA antibodies have the most significant differences. Moreover, we further analyzed cytokine expression between these two groups. A wide variety of cytokines presented high expression in the infected individuals, while a few cytokines were elicited by inactivated vaccines. The differences in antibody responses and cytokine levels between natural SARS-CoV-2 infection and vaccination with the inactivated vaccines may provide implications for the optimization of inactivated SARS-CoV-2 vaccines and the additional application of serological tests.

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Enhanced Immunogenicity of a Whole-Inactivated Influenza A Virus Vaccine Using Optimised Irradiation Conditions

Cited by 4 publications

References 35 publications

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

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

Low-Energy Electron Irradiation of Tick-Borne Encephalitis Virus Provides a Protective Inactivated Vaccine

Distinct immune responses in the early phase to natural SARS‐CoV‐2 infection or vaccination

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