Novel Virus-Like Particle Vaccine Encoding the Circumsporozoite Protein of Plasmodium falciparum Is Immunogenic and Induces Functional Antibody Responses in Mice
نویسندگان
چکیده
RTS,S is the leading malaria vaccine in development, but has demonstrated only moderate protective efficacy clinical trials. a virus-like particle (VLP) that uses human hepatitis B virus as scaffold to display sporozoite antigen, circumsporozoite protein (CSP). Particle formation requires four-fold excess and result, CSP represents small portion of final construct. Alternative VLP or nanoparticle platforms reduce amount antigen increase target present particles may enhance immunogenicity efficacy. Here, we describe production characterization novel surface (dS) duck CSP. The CSP-dS fusion successfully formed VLPs without need for thus represented larger large approximately 31-74 nm size were confirmed on surface. highly immunogenic mice induced antibodies multiple regions CSP, even when administered at lower dosage. Vaccine-induced relevant functional activities, including Fc-dependent interactions with complement Fc?-receptors, previously identified important immunity. Further, vaccine-induced had similar properties (epitope-specificity avidity) monoclonal are mouse models. Our platform produce wide implications future development vaccines other infectious diseases.
منابع مشابه
Protective Antibody and CD8+ T-Cell Responses to the Plasmodium falciparum Circumsporozoite Protein Induced by a Nanoparticle Vaccine
BACKGROUND The worldwide burden of malaria remains a major public health problem due, in part, to the lack of an effective vaccine against the Plasmodium falciparum parasite. An effective vaccine will most likely require the induction of antigen specific CD8(+) and CD4(+) T-cells as well as long-lasting antibody responses all working in concert to eliminate the infection. We report here the eff...
متن کاملPhase I Trial of an Alhydrogel Adjuvanted Hepatitis B Core Virus-Like Particle Containing Epitopes of Plasmodium falciparum Circumsporozoite Protein
UNLABELLED The objectives of this non-randomized, non-blinded, dose-escalating Phase I clinical trial were to assess the safety, reactogenicity and immunogenicity of ICC-1132 formulated with Alhydrogel (aluminum hydroxide) in 51 healthy, malaria-naive adults aged 18 to 45 years. ICC-1132 (Malariavax) is a recombinant, virus-like particle malaria vaccine comprised of hepatitis core antigen engin...
متن کاملMonoclonal Antibodies against Plasmodium falciparum Circumsporozoite Protein
Malaria is a mosquito-borne infectious disease caused by the parasite Plasmodium spp. Malaria continues to have a devastating impact on human health. Sporozoites are the infective forms of the parasite inside mosquito salivary glands. Circumsporozoite protein (CSP) is a major and immunodominant protective antigen on the surface of Plasmodium sporozoites. Here, we report a generation of specific...
متن کاملVariation in the Circumsporozoite Protein of Plasmodium falciparum: Vaccine Development Implications
The malaria vaccine candidate RTS,S/AS01 is based on immunogenic regions of Plasmodium falciparum circumsporozoite protein (CSP) from the 3D7 reference strain and has shown modest efficacy against clinical disease in African children. It remains unclear what aspect(s) of the immune response elicited by this vaccine are protective. The goals of this study were to measure diversity in immunogenic...
متن کاملStructural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein
Acquired resistance against antimalarial drugs has further increased the need for an effective malaria vaccine. The current leading candidate, RTS,S, is a recombinant circumsporozoite protein (CSP)-based vaccine against Plasmodium falciparum that contains 19 NANP repeats followed by a thrombospondin repeat domain. Although RTS,S has undergone extensive clinical testing and has progressed throug...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Frontiers in Immunology
سال: 2021
ISSN: ['1664-3224']
DOI: https://doi.org/10.3389/fimmu.2021.641421