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Comparative Study of the Immune Responses to the Hms-Based Fusion Protein and Capsule-Based Conjugated Molecules As Vaccine Candidates in a Mouse Model of Staphylococcus Aureus Systemic Infection Publisher Pubmed



Ahmadi K1 ; Hasaniazad M1 ; Kalani M2 ; Faezi S3 ; Ahmadi N4 ; Enayatkhani M5 ; Mahdavi M6, 7, 8 ; Pouladfar G2
Authors
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Authors Affiliations
  1. 1. Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
  2. 2. Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  3. 3. Medical Biotechnology Research Center, School of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
  4. 4. Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Molecular Medicine Department, Biotechnology Research Centre, Pasteur Institute of Iran, Tehran, Iran
  6. 6. Recombinant Vaccine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Immunotherapy Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Immunology, Pasteur Institute of Iran, Tehran, Iran

Source: Microbial Pathogenesis Published:2021


Abstract

Staphylococcus aureus is a powerful pathogen that causes a wide range of infectious diseases and results in a high mortality rate in humans. Treating S. aureus-related infections is extremely difficult because of its ability to resist many antibiotics; therefore, developing an effective vaccine against this infection can be an alternative and promising approach. In this study, we evaluated the protective effects of a Hla-MntC-SACOL0723 multi-epitope protein (HMS) compared with HMS conjugated to polysaccharides 5 and 8 (CP5 and CP8) of S. aureus and CP5 and CP8 in a mouse sepsis model. To evaluate the type of induced immune response, specific IgG, and antibody isotypes (IgG1 and IgG2a) were determined using the ELISA method. The functional activity of these vaccine candidates was assessed by opsonophagocytosis. Mice were infected with S. aureus COL strain and evaluated for bacterial load in the kidney and spleen homogenates. Th1, Th2, and Th17-related cytokines in the spleen cell supernatants were assessed by flow cytometry. The therapeutic effect of specific anti-HMS protein IgG antibodies against S. aureus COL strain infection was evaluated by passive immunization. HMS recombinant protein induced a higher level of Th1, Th2, and Th17-related cytokines compared with conjugated molecules. Also, mice immunized with the HMS protein reduced the bacterial load in the kidney and spleen more than the one that received the conjugated molecules. Our study suggests that the HMS fusion protein and conjugate molecule vaccine candidates could be suitable candidates for the removal of S. aureus in the mouse sepsis model but HMS protein can be a more effective candidate. © 2020