Abstract
BackgroundSeveral studies on gamma-irradiated influenza A virus (γ-Flu) have revealed its superior efficacy for inducing homologous and heterologous virus-specific immunity. However, many inactivated vaccines, notably in nasal delivery, require adjuvants to increase the quality and magnitude of vaccine responses.MethodsTo illustrate the impacts of co-administration of the gamma-irradiated H1N1 vaccine with poly (I:C) and recombinant murine CCL21, either alone or in combination with each other, as adjuvants on the vaccine potency, mice were inoculated intranasally 3 times at one-week interval with γ-Flu alone or with any of the three adjuvant combinations and then challenged with a high lethal dose (10 LD50) of A/PR/8/34 (H1N1) influenza virus. Virus-specific humoral, mucosal, and cell-mediated immunity, as well as cytokine profiles in the spleen (IFN-γ, IL-12, and IL-4), and in the lung homogenates (IL-6 and IL-10) were measured by ELISA. The proliferative response of restimulated splenocytes was also determined by MTT assay.ResultsThe findings showed that the co-delivery of the γ-Flu vaccine and CCL21 or Poly (I:C) significantly increased the vaccine immunogenicity compared to the non-adjuvanted vaccine, associated with more potent protection following challenge infection. However, the mice given a combination of CCL21 with poly (I:C) had strong antibody- and cell-mediated immunity, which were considerably higher than responses of mice receiving the γ-Flu vaccine with each adjuvant separately. This combination also reduced inflammatory mediator levels (notably IL-10) in lung homogenate samples.ConclusionsThe results indicate that adjuvantation with the CCL21 and poly (I:C) can successfully induce vigorous vaccine-mediated protection, suggesting a robust propensity for CCL21 plus poly (I:C) as a potent mucosal adjuvant.
Highlights
IntroductionAppropriate inactivation techniques, which abolish viral infectious titers while preserving the immunogenicity of Sabbaghi et al Virol J (2021) 18:201 cross-reactivity, due to the ability of gamma-rays to preserve most of the antigenic structure and biological integrity of proteins during treatment, making it a promising vaccine candidate to overcome the low efficacy of current Flu-vaccines against antigenic variants of influenza virus [1,2,3,4,5,6].More importantly, radiation conditions including gamma-irradiation dose and the temperature of radiation, -as well as the Bremsstrahlung process, the secondary radiation produced during treatment with gamma-irradiation, may introduce unwanted structural damages in viral proteins upon the pathogen inactivation [6, 7]
Chemokine ligand 21 (CCL21)‐Poly (I:C) adjuvanted vaccine improved systemic antibodies and cell‐mediated immunity in mice To characterize the mucosal adjuvant efficacy of murine recombinant CCL21 and Poly (I:C) for γ-inactivated influenza A vaccine, immunoglobulin G antibodies were examined in the sera collected from mice inoculated intranasally 3 times at one-week interval with Gamma-irradiated influenza A virus (γ-Flu), γ-Flu-CCL21, γ-Flu-Poly (I:C), or γ-FluCCL21-Poly (I:C)
Our data illustrated the significant enhancement of influenza-specific total IgG titer in mice immunized with either γ-Flu alone or with any of the three adjuvant combinations compared to mice treated with CCL21, Poly (I:C), and PBS (p < 0.001)
Summary
Appropriate inactivation techniques, which abolish viral infectious titers while preserving the immunogenicity of Sabbaghi et al Virol J (2021) 18:201 cross-reactivity, due to the ability of gamma-rays to preserve most of the antigenic structure and biological integrity of proteins during treatment, making it a promising vaccine candidate to overcome the low efficacy of current Flu-vaccines against antigenic variants of influenza virus [1,2,3,4,5,6].More importantly, radiation conditions including gamma-irradiation dose and the temperature of radiation, -as well as the Bremsstrahlung process, the secondary radiation produced during treatment with gamma-irradiation, may introduce unwanted structural damages in viral proteins upon the pathogen inactivation [6, 7]. Appropriate inactivation techniques, which abolish viral infectious titers while preserving the immunogenicity of Sabbaghi et al Virol J (2021) 18:201 cross-reactivity, due to the ability of gamma-rays to preserve most of the antigenic structure and biological integrity of proteins during treatment, making it a promising vaccine candidate to overcome the low efficacy of current Flu-vaccines against antigenic variants of influenza virus [1,2,3,4,5,6]. Adverse effects of non-optimized experimental inactivation conditions, such as high radiation dose and high temperature, on the immunogenicity of the γ-Flu vaccine have been evaluated [6]. Mucosal immunization by intranasal administration of inactivated vaccines without appropriate mucosal adjuvants is often not sufficiently effective [8,9,10]. Many inactivated vaccines, notably in nasal delivery, require adjuvants to increase the quality and magnitude of vaccine responses
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