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A Formulated Poly (I:C)/Ccl21 As an Effective Mucosal Adjuvant for Gamma-Irradiated Influenza Vaccine Publisher Pubmed



Sabbaghi A1 ; Malek M2 ; Abdolahi S3 ; Miri SM1 ; Alizadeh L3 ; Samadi M4 ; Mohebbi SR4, 5 ; Ghaemi A1
Authors
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Authors Affiliations
  1. 1. Department of Influenza and Other Respiratory Viruses, Pasteur Institute of Iran, P.O.Box: 1316943551, Tehran, Iran
  2. 2. Department of Microbiology, Science and Research Branch, Islamic Azad University, Tehran, Iran
  3. 3. Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran
  4. 4. Department of Medical Virology, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Source: Virology Journal Published:2021


Abstract

Background: Several 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. Methods: To 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. Results: The 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. Conclusions: The 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. © 2021, The Author(s).
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