Abstract
Due to the increasing amount of people afflicted worldwide with Chagas disease and an increasing prevalence in the United States, there is a greater need to develop a safe and effective vaccine for this neglected disease. Adenovirus serotype 5 (Ad5) is the most common adenovirus vector used for gene therapy and vaccine approaches, but its efficacy is limited by preexisting vector immunity in humans resulting from natural infections. Therefore, we have employed rare serotype adenovirus 48 (Ad48) as an alternative choice for adenovirus/Chagas vaccine therapy. In this study, we modified Ad5 and Ad48 vectors to contain T. cruzi’s amastigote surface protein 2 (ASP-2) in the adenoviral early gene. We also modified Ad5 and Ad48 vectors to utilize the “Antigen Capsid-Incorporation” strategy by adding T. cruzi epitopes to protein IX (pIX). Mice that were immunized with the modified vectors were able to elicit T. cruzi-specific humoral and cellular responses. This study indicates that Ad48-modified vectors function comparable to or even premium to Ad5-modified vectors. This study provides novel data demonstrating that Ad48 can be used as a potential adenovirus vaccine vector against Chagas disease.
Highlights
Chagas disease (American trypanosomiasis) is one of the 17 neglected tropical diseases (NTDs) affecting the world today [1,2]
T. cruzi is transmitted to the mammalian host at the site of a triatomine bug bite [4]. (CD) is an illness that once was only common in the Latin America region [4], the disease is responsible for 10–50,000 deaths/year and infecting 12–20 million people worldwide [5]
Adenovirus serotype 5 (Ad5) and adenovirus 48 (Ad48) vectors that have an immunodominant CD8 T-cell epitope (VNHRFTLV) from the carboxyl-terminal region of amastigote surface protein 2 (ASP-2) as well as a FLAG (DYKDDDDK) epitope incorporated into the minor Ad capsid protein IX (Figure 1C,G)
Summary
Chagas disease (American trypanosomiasis) is one of the 17 neglected tropical diseases (NTDs) affecting the world today [1,2]. Chagas disease (CD) [3]. (CD) is an illness that once was only common in the Latin America region [4], the disease is responsible for 10–50,000 deaths/year and infecting 12–20 million people worldwide [5]. Chagas disease has two clinical stages, acute and chronic stage [6]. The acute stage occurs after initial infection but often goes unobserved due to mild symptoms [7]. Nifurtimox and Benznidazol are current treatments for this infection [9]. These anti-parasitic drugs are 80% successful in curing the acute phase with severe side effects. When the acute stage is untreated, the disease becomes chronic [7], anti-parasitic drugs are ineffective in curing the chronic phase
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
