Objective This study aimed to investigate the effects of Montanide ISA-720 and Naloxone (NLX) in Hepatitis B surface antigen (HBsAg) vaccine formulation on cytokine and long-lasting antibody responses. Methods First, the HBsAg was formulated in Montanide ISA-720 adjuvant and Naloxone at 5 and 10 mg/kg. The experimental mice were immunized three times at a 2-week interval, and then IL-4, IL-2, TNF-α, and IFN-γ cytokines; long-lasting IgG antibody responses 220 days after the last shot; and IgG1/IgG2a isotypes were assessed by ELISA. Results The HBsAg-Alum group exhibited the highest IL-4 cytokine response among the experimental groups, whereas NLX in HBsAg-MON720 vaccine formulation did not affect cytokine responses. In addition, NLX in Alum-based vaccine suppressed IL-4 cytokine response and increased the IL-2/IL-4 cytokine ratio. Moreover, HBsAg-MON720 was more potent than HBsAg-Alum in the induction of antibody responses, and NLX in Alum- and MON720-based vaccines induced long-lasting antibody responses. Conclusion NLX in Alum-based vaccine decreased IL-4 cytokine response, increased IL-2/IL-4 cytokine ratio, and improved long-lasting humoral immune responses in both vaccine formulations. Therefore, the adjuvant activity of NLX in the vaccine formulation depends on the type of adjuvant and the nature of the antigen in the vaccine formulation.

Mina Mirzaee;Setareh Haghighat;Bahareh Golkaran;Fatemeh Asgarhalvaei;Rayhaneh Mirzaee;Morteza Taghizadeh;Mohammad Ali Savoji;Behzad Esfandiari;Mehdi Mahdavi

Department of Microbiology,Faculty of Advanced Sciences&Technology,Tehran Medical Sciences,Islamic Azad University,(IAUPS),Tehran,Iran;Department of Biotechnology,Faculty of Advanced Sciences&Technology, Pharmaceutical Sciences Branch,Islamic Azad University,Tehran-Iran(IAUPS;Department of Medical vaccine, Razi Vaccine and Serum Research Institute,Agricultural Research,Education and Extension Organization(AREEO), Karaj,Iran;Department of Epidemiology and Biostatistics,Pasteur Institute of Iran,Tehran,Iran;Department of Laboratory Animal Science,Pasteur Institute of Iran,Karaj,Iran;Advanced Therapy Medicinal Product (ATMP)Department,Breast Cancer Research Center,Motamed Cancer Institute,Academic Center for Education, Culture and Research(ACECR),Tehran,Iran;Recombinant Vaccine Research Center,Tehran University of Medical Sciences,Tehran,Iran;Department of Immunology,Pasteur Institute of Iran,Tehran,Iran;Immunotherapy Group,The Institute of Pharmaceutical Sciences(TIPS),Tehran University of Medical Sciences, Tehran,Iran

生物医学与环境科学（英文版）

[1]Mina Mirzaee;Setareh Haghighat;Bahareh Golkaran;Fatemeh Asgarhalvaei;Rayhaneh Mirzaee;Morteza Taghizadeh;Mohammad Ali Savoji;Behzad Esfandiari;Mehdi Mahdavi-.Montanide ISA-720 and Naloxone in HBsAg Vaccine Formulation: Cytokine Profiling and Monitoring of Long-Lasting Humoral Immune Responses)[J].生物医学与环境科学（英文版）,2022(09):792-803

Montanide,Humoral,isotypes,MON720

Naloxone,HBsAg,Vaccine,Formulation,Cytokine,Profiling,Monitoring,Long,Lasting,Immune,Responses,Objective,This,study,aimed,investigate,effects,NLX,Hepatitis,surface,antigen,long,lasting,antibody,responses,Methods,First,was,formulated,adjuvant,experimental,mice,were,immunized,three,times,week,interval,then,IFN,cytokines,days,after,shot,IgG1,IgG2a,assessed,by,Results,Alum,exhibited,highest,among,groups,whereas,did,not,affect,In,addition,suppressed,increased,ratio,Moreover,more,potent,than,induction,vaccines,induced,Conclusion,decreased,improved,humoral,immune,both,formulations,Therefore,activity,depends,nature

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