الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Hepatitis A Is A Highly Infectious Liver Disease Caused By A Very Stable Virus Transmitted Via The Fecal-Oral Route. Hepatitis A Occurs Most Often In Areas With Inadequate Sanitation. The Disease’s Effects Can Be Substantial And Cause Considerable Economic And Social Damage To Communities. However, Hepatitis A Is A Preventable Disease, And Vaccination Is The Only Way To Prevent Hepatitis A.
Cholera Is Acute Gastroenteritis Caused By The Vibrio Cholerae Serogroups O1 Or O139 Bacteria. Infection Induces Excessive Watery Diarrhea, And Up To 40% Of Untreated Patients Die. Protective Immunity To Cholera Is Specific To Vibrio Cholerae Serogroup. Recent Epidemics Of Cholera Have Shown That An Effective Vaccine Against This Severe Disease Is Still Needed.
Adjuvants Are Essential For Improving And Directing The Adaptive Immunity To Vaccine Antigens. Despite The Fact That, Alum Is The Most Commonly Used Adjuvant, It Provides Some Challenges That Require Resolving. Alternatively, Two Natural Adjuvant Candidates Are Showing The Better Performance (I.E., Chitosan And Alginate Salts), where Many Studies Exhibited Significant Supporting Evidence As Adjuvants And They Do Not Produce Toxicity In Administration. There Is Also A Growing Trend Towards The Production Of A Polymeric Microparticle Adjuvant, Such As Alginate-Chitosan-Based Microspheres. These Microparticles Encapsulate The Antigens, And Offer A Vaccine Delivery System That Enhances The Immune Response.
In The Present Study, We Assessed The Improvement Of The Immune Response Of Both Inactivated Cholera And HAV Vaccines Using Different Adjuvants By Preparing Different Formulation Of HAV With Either Alum, Chitosan Or Alginate Coated Chitosan Nanoparticles, And Cholera Vaccine With Alum, Chitosan Or Sodium Alginate Using Balb/C Mice As The Animal Model. The Different Formulations Were Injected Interperitoneally To Animal group (8 Mice/ Group) Besides A Control group Injected With Saline Only. The Mice In Each group Were Under Observation For 14 Days To Evaluate The Safety Of Each Formulation. The Mice Were Sacrificed After 28±2 Days And Sera Were Collected. Each group Was Subjected To Further Analysis To Assess Their Immune Response As The Rate Of Positive Seroconversion, Total Anti-Specific Igg And Igg Subclasses (Igg1and Igg2a), Lymphoproliferation Assay, Cytokines Assays (IL2, IL-4, IL10 And IFN-), And Challenge Assay Against Cholera Strains. All The Formulations, Whether Combined Or Adjuvanted, Showed Neither Mortality Nor Signs Of Ill-Health Or Inflammation Issues For 14 Days.
Regarding The Single Adjuvanted HAV Formulations, The Presence Of Chitosan Also Increased The HAV-Specific Levels Of Antibodies Relative To The Recorded Levels In HAV And HAV-Al Groups. The Same Findings Were Extended To The Cellular Immune Response, As Shown By Induced Splenocyte Proliferation. All Of The Above Findings Indicated That Chitosan Could Be A Suitable Substitute For Alum As An Adjuvant To HAV. Loading HAV With The Alginate-Coated Chitosan Nanoparticles Intensified The Immune Response To Hepatitis A. This Immune Defense Was Expressed In The Total HAV-Specific Antibodies. HAV-Acnp ’S Dominance In The Cellular Immune Response Has Been Proved Once Again. Nevertheless Again, Cytokine Analysis Confirmed The Influence Of Alginate-Chitosan Nanoparticles On The Immune Pathways Th1 And Th2.
Regarding The Single Adjuvanted Cholera Formulations, The Cholera Vaccine Adjuvanted With Alum Gave Proper Immune Response Compared To Other Adjuvanted Formulations. The Total Antibodies-Specific Against Cholera Strains Was Insignificantly Higher Than The Antibodies In ICV Group. Finally, The Addition Of Alum Enhanced The Survival Rate Of The Vaccinated Mice Against The Cholera Strain Combined. Using Chitosan As An Adjuvant For Cholera Vaccine Improved The Immune Response Remarkably. The Humoral Immune Response Elevated Significantly Against Inaba Strain. The Proliferation Response In The Adjuvanted Chitosan group Slightly Increased Compared To ICV Group. The Survival Rate In The ICV-Ch group Was Tremendously Higher Among The Other Groups (ICV, ICV-Al, And ICV-SS). The Effect Of S.Alginate On The Cholera Vaccine Substantially Increased The Immune Response. Igg Was Augmented When Compared To The Cholera Vaccine Alone For Both Strains. Also, It Significantly Increased The Proliferation Of The Cells Against Cholera Strains. The Survival Rate Against The Cholera Challenge In ICV-SS Was Significantly Higher Than ICV And ICV-Al But Remarkably Lower Than ICV-Ch.
In Our Study, We Aimed To Evaluate The Safety Profile And Immune Responses Of The Combination Of Inactivated Cholera And HAV Vaccines Into A Single Vaccine In A Murine Model. First, We Measured The Effect Of The Combined Vaccine On HAV Immunogenic Response. The Combined Vaccine Preparation, Whether Adjuvanted Or Unadjuvanted, Boosted The Immune Response Significantly On The Humoral And Cellular Levels. We Can Conclude That Solution Combined Vaccine Adjuvanted With Chitosan Has The Most Substantia Antibody-Mediated Response Among The Other Combined Groups. On The Other Hand, The Unadjuvanted Combined group ICV-HAV Exhibited A Powerful Cellular Immune Response. The Same Effect Observed On The Cholera Side, where The Combination Of HAV With Cholera Augmented The Humoral Immune Response As The Total Igg Against The Cumulative Cholera Strains Was Significantly Higher Than Uncombined Cholera Vaccinated Group. However, The Adjuvanted Combined Vaccine Formulations Produced Equivalent Titers Of Total Igg To The Unadjuvanted One. Adjuvanted Combined Solution Formulation Had The Most Significant Proliferation Response Even Compared To The Other Combined Formulations. At Last, As Expected, The Combined Formulations Enhanced The Survival Rates Significantly Against Cholera Strains When Compared To The Other Cholera Vaccines. ICV-HAV, In Particular, Exhibited The Highest Survival Rate Among All The Cholera Vaccinated Groups. Based On The Mentioned Results, It Appears That The Combination Of Inactivated Cholera And HAV Vaccine Had A Synergistic Effect And Enhanced The Immune Response Towards Both HAV And Cholera Strains.