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Ascorbic Acid and Α-Tocopherol in the Inactivated Sars-Cov-2 Vaccine Formulation: Induction of the Th1 Pattern in Aged Mice Publisher Pubmed



Asefi N1, 2 ; Pakzad P1 ; Khorasani A3 ; Taghizadeh M4 ; Amirkhani Z5 ; Yazdi MH6, 7 ; Shahverdi AR6, 8 ; Mahdavi M2, 7
Authors
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Authors Affiliations
  1. 1. Department of Microbiology, Faculty of Basic Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
  2. 2. Advanced Therapy Medicinal Product (ATMP) Department, Breast Cancer Research Center, Academic Center for Education, Culture and Research (ACECR), Motamed Cancer Institute, Tehran, Iran
  3. 3. Department of FMD vaccine production, Razi Vaccine & Serum Research Institute, Agricultural Research, Education & Extension Organization (AREEO), Karaj, Iran
  4. 4. Department of Human Vaccine, Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization (AREEO), Karaj, Iran
  5. 5. Cellular and Molecular Biology Research Center, Larestan University of Medical Sciences, Larestan, Iran
  6. 6. Biotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Recombinant Vaccine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Viral Immunology Published:2024


Abstract

Aging is physiologically associated with a decline in the function of the immune system and subsequent susceptibility to infections. Interferon-gamma (IFN-γ), a key element in the activation of cellular immunity, plays an important role in defense against virus infections. Decreased levels of IFN-γ in the elderly may explain their increased risk for viral infectious diseases such as COVID-19. There is accumulating evidence that ascorbic acid (vitamin C [VitC]) and α-tocopherol together help improve the function of the immune system in the elderly, control infections, and decrease the treatment duration. A SARS-CoV-2 strain was isolated from a patient and then cultured in the Vero cell line. The isolated and propagated virus was then inactivated using formalin and purified by the column chromatography. The inactivated SARS-CoV-2 was formulated in the Alum adjuvant combined with VitC or α-tocopherol and/or both of them. The vaccines were injected twice to young and aged C57BL/6 mice. Two weeks later, IFN-γ, IL-4, and IL-2 cytokines were assessed using ELISA Kits. Specific IgG and IgG1/IgG2a were assessed by an in-house ELISA. In addition, the expression of PD1 and TERT genes in the spleen tissue of the mice was measured using real-time PCR. IL-4 and IFN-γ cytokines showed a significant increase in both aged and young mice compared with the Alum-based vaccine. In addition, our results exhibited a significant decrease and increase in specific total IgG and the IgG2a/IgG1 ratio, respectively. Furthermore, the vaccine formulated in α-tocopherol + VitC led to decreased PD1 and increased TERT gene expression levels. In conclusion, our results demonstrated that α-tocopherol + VitC formulated in the inactivated SARS-CoV-2 vaccine led to a shift toward Th1, which may be due to their effect on the physiology of cells, especially aged ones and changing their phenotype toward young cells. Copyright 2024, Mary Ann Liebert, Inc., publishers.
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