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Emerg Microbes Infect ; 10(1): 365-375, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1490458


Concerns about vaccine safety are an important reason for vaccine hesitancy, however, limited information is available on whether common adverse reactions following vaccination affect the immune response. Data from three clinical trials of recombinant vaccines were used in this post hoc analysis to assess the correlation between inflammation-related solicited adverse reactions (ISARs, including local pain, redness, swelling or induration and systematic fever) and immune responses after vaccination. In the phase III trial of the bivalent HPV-16/18 vaccine (Cecolin®), the geometric mean concentrations (GMCs) for IgG anti-HPV-16 and -18 (P<0.001) were significantly higher in participants with any ISAR following vaccination than in those without an ISAR. Local pain, induration, swelling and systemic fever were significantly correlated with higher GMCs for IgG anti-HPV-16 and/or anti-HPV-18, respectively. Furthermore, the analyses of the immunogenicity bridging study of Cecolin® and the phase III trial of a hepatitis E vaccine yielded similar results. Based on these results, we built a scoring model to quantify the inflammation reactions and found that the high score of ISAR indicates the strong vaccine-induced antibody level. In conclusion, this study suggests inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.

Hepatitis E/immunology , Human papillomavirus 16/immunology , Human papillomavirus 18/immunology , Papillomavirus Infections/immunology , Papillomavirus Vaccines/immunology , Vaccines, Synthetic/immunology , Viral Hepatitis Vaccines/immunology , Adolescent , Adult , Aged , Antibodies, Viral/immunology , Female , Hepatitis E/prevention & control , Hepatitis E/virology , Human papillomavirus 16/genetics , Human papillomavirus 18/genetics , Humans , Immunity , Immunoglobulin G/immunology , Male , Middle Aged , Papillomavirus Infections/prevention & control , Papillomavirus Infections/virology , Papillomavirus Vaccines/administration & dosage , Papillomavirus Vaccines/adverse effects , Papillomavirus Vaccines/genetics , Vaccination/adverse effects , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/genetics , Viral Hepatitis Vaccines/administration & dosage , Viral Hepatitis Vaccines/adverse effects , Viral Hepatitis Vaccines/genetics , Young Adult
Int J Mol Sci ; 22(13)2021 Jun 26.
Article in English | MEDLINE | ID: covidwho-1304664


Hepatitis C virus (HCV) is one of the main triggers of chronic liver disease. Despite tremendous progress in the HCV field, there is still no vaccine against this virus. Potential vaccines can be based on its recombinant proteins. To increase the humoral and, especially, cellular immune response to them, more effective adjuvants are needed. Here, we evaluated a panel of compounds as potential adjuvants using the HCV NS5B protein as an immunogen. These compounds included inhibitors of polyamine biosynthesis and urea cycle, the mTOR pathway, antioxidants, and cellular receptors. A pronounced stimulation of cell proliferation and interferon-γ (IFN-γ) secretion in response to concanavalin A was shown for antioxidant N-acetylcysteine (NAC), polyamine biosynthesis inhibitor 2-difluoromethylornithine (DFMO), and TLR9 agonist CpG ODN 1826 (CpG). Their usage during the immunization of mice with the recombinant NS5B protein significantly increased antibody titers, enhanced lymphocyte proliferation and IFN-γ production. NAC and CpG decreased relative Treg numbers; CpG increased the number of myeloid-derived suppressor cells (MDSCs), whereas neither NAC nor DFMO affected MDSC counts. NAC and DFMO suppressed NO and interleukin 10 (IL-10) production by splenocytes, while DFMO increased the levels of IL-12. This is the first evidence of immunomodulatory activity of NAC and DFMO during prophylactic immunization against infectious diseases.

Acetylcysteine/pharmacology , Adjuvants, Immunologic/pharmacology , Eflornithine/pharmacology , Hepatitis C/immunology , Immunity, Active/drug effects , Viral Nonstructural Proteins/immunology , Animals , Cell Proliferation , Cells, Cultured , Female , Immunogenicity, Vaccine/drug effects , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-12/metabolism , Mice , Mice, Inbred DBA , Myeloid-Derived Suppressor Cells/drug effects , Myeloid-Derived Suppressor Cells/immunology , Nitric Oxide/metabolism , Oligodeoxyribonucleotides/pharmacology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Viral Hepatitis Vaccines/immunology