Alginate-coated chitosan nanoparticles act as effective adjuvant for hepatitis A vaccine in mice Nourhan H. AbdelAllah a,b , Yasser Gaber a,c , Mohamed E. Rashed e , Ahmed F. Azmy a , Heba A. Abou-Taleb d , Sameh AbdelGhani a,f, ⁎ a Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, 62511 Beni-Suef, Egypt b Viral Control Unit, National Organization for Research and Control of Biologicals (NORCB), Cairo 12654, Egypt c Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Mutah University, Al-karak 61710, Jordan d Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Nahda University (NUB), Beni-Suef, Egypt e Microbiology Department, National Organization for Research and Control of Biologicals (NORCB), Cairo 12654, Egypt f Department of Pathology and Medical Laboratory, University of Louisville, KY 40202, USA abstract article info Article history: Received 16 January 2020 Received in revised form 24 February 2020 Accepted 25 February 2020 Available online 27 February 2020 Keywords: Hepatitis A Vaccine Chitosan Alginate Nanoparticles The numerous recent hepatitis A outbreaks emphasize the need for vaccination; despite the effectiveness of the current ones, developments are needed to overcome its high cost plus some immune response limitations. Our study aims to evaluate the use of chitosan and alginate-coated chitosan nanoparticles as an adjuvant/carrier for the hepatitis A vaccine (HAV) against the traditional adjuvant alum. Immune responses towards (HAV-Al) with alum, (HAV-Ch) with chitosan, and (HAV-aCNP) with alginate-coated chitosan nanoparticles, were assessed in mice. HAV-aCNP significantly improved the immunogenicity by increasing the seroconversion rate (100%), the hepatitis A antibodies level, and the splenocytes proliferation. Thus, the HAV-aCNP adjuvant was superior to other classes in IFN-γ and IL-10 development. Meanwhile, the solution formula of HAV with chitosan showed comparable humoral and cellular immune responses to alum-adjuvanted suspension with a balanced Th1/Th2 immune pathway. The current study showed the potential of alginate-coated chitosan nanoparticles as an effec- tive carrier for HAV. Consequently, this would impact the cost of HAV production positively. © 2020 Elsevier B.V. All rights reserved. 1. Introduction Hepatitis A is considered one of the highly contagious liver diseases caused by a very stable virus that passes through the fecal-oral route. It is most commonly occurring in areas of poor hygiene and low socioeco- nomic conditions. About 20% to 25% of hepatitis cases were related to hepatitis A in developed countries with poor sanitary conditions and hygienic practices [1]. The infection is common in children under the age of 10 years. In middle and high-income countries, the infection rates occur among adolescents, older age, and high-risk adults' groups. Also, the disease can spread among travelers to areas of high endemic- ity, and in isolated populations. United States of America reported sev- eral outbreaks of hepatitis A from 2013 to 2018 [2–5]. It is rarely fatal, and the severity of infection is usually increasing with age. Only a small percentage (b1%) of the infected patients, especially older adults or people with chronic liver diseases, die of fulminant hepatitis, for ex- ample, in 2016, WHO announced that N7000 people had been died due to hepatitis A [3,6]. The impact of the disease can be substantial and lead to significant loss to communities economically and socially. However, hepatitis A is a preventable disease, and the best way to pre- vent it is through vaccination. An effective and safe vaccine for hepatitis A is available; the formaldehyde-inactivated vaccines are widely used in most countries. It was estimated that two-dose is sufficient to acquire long-lasting im- munity for N20 years. However, the vaccination schedule was based on the results from mathematical models, and till now, the antibody levels are not indicative enough to prove the efficiency of the schedule [7]. Besides, the antibodies titer of chronic liver disease patients was ob- served to be lower than the titer of healthy people [8,9]. Similarly, the same observations were studied in human immunodeficiency virus (HIV) patients, and the rates of seroconversion were somewhat higher in non-HIV-infected individuals compared with HIV patients [10,11]. Adjuvants play an essential role in the formulation and efficacy of HAV, aluminum hydroxide (alum) is the currently adjuvant used to am- plify the immune response of the inactivated hepatitis A vaccine. Al- though alum is cost-effective and easy to apply in the manufacturing process, it has some disadvantages. These disadvantages are related to the safety and efficacy of adjuvanted alum vaccine. The safety issues, in- cluding inflammations and other clinical reactions, have been detected in different studies [12,13], while the efficacy obstacles related to its International Journal of Biological Macromolecules 152 (2020) xxx ⁎ Corresponding author at: Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, 62511 Beni-Suef, Egypt. E-mail address: sameh.abdelghani@pharm.bsu.edu.eg (S. AbdelGhani). BIOMAC-14904; No of Pages 9 https://doi.org/10.1016/j.ijbiomac.2020.02.287 0141-8130/© 2020 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect International Journal of Biological Macromolecules journal homepage: http://www.elsevier.com/locate/ijbiomac Please cite this article as: N.H. AbdelAllah, Y. Gaber, M.E. Rashed, et al., Alginate-coated chitosan nanoparticles act as effective adjuvant for hepatitis A vaccine in mice, https://doi.org/10.1016/j.ijbiomac.2020.02.287