Vaccine Efficacy against Malaria by the Combination of Porcine Parvovirus-Like Particles and Vaccinia Virus Vectors Expressing CS of Plasmodium

Abstract

With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs) carrying the CD8+ T cell epitope (SYVPSAEQI) of the circumsporozoite (CS) protein from Plasmodium yoelii fused to the PPV VP2 capsid protein (PPV-PYCS), and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8+ T cell response elicited by these hybrid PPV-VLPs in BALB/c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus (VACV) vectors from the Western Reserve (WR) and modified virus Ankara (MVA) strains expressing the entire P. yoelii CS protein. The results of different immunization protocols showed that the combination of PPV-PYCS prime/poxvirus boost was highly immunogenic, inducing specific CD8+ T cell responses to CS resulting in 95% reduction in liver stage parasites two days following sporozoite challenge. In contrast, neither the administration of PPV-PYCS alone nor the immunization with the vectors given in the order poxvirus/VLPs was as effective. The immune profile induced by VLPs/MVA boost was associated with polyfunctional and effector memory CD8+ T cell responses. These findings highlight the use of recombinant parvovirus PPV-PYCS particles as priming agents and poxvirus vectors, like MVA, as booster to enhance specific CD8+ T cell responses to Plasmodium antigens and to control infection. These observations are relevant in the design of T cell-inducing vaccines against malaria.

Vaccination Using Recombinants Influenza and Adenoviruses Encoding Amastigote Surface Protein-2 Are Highly Effective on Protection against Trypanosoma cruzi Infection

“…However, while the role of different T cell subpopulation to control the infection with some viruses, bacteria and Plasmodium was already well documented [47], [48], [49], [50], the biological relevance of CD8+ T cells subpopulations phenotypes to control the infection with T. cruzi remains elusive [51]. The IFN-γ production itself is known to be important for protection against Trypanosoma cruzi infection in many previous work of our and other groups [14], [52], [53], [54], [55].…”

Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors

“…It may also be important in the later selection of the recombinant viruses obtained. For instance, inserting the gene of interest in the thymidine kinase ( TK ) locus confers a detectable phenotype (TK-): the recombinant viruses are able to grow in the presence of 5-bromo-2’-deoxyuridine (BrdU), a synthetic analog of thymidine [ 28 , 34 ]. Another important site of insertion that allows a subsequent selection is the VACV hemagglutinin ( HA ) gene as the recombinant viruses can be easily recognized by their disability to bind erythrocytes in a hemagglutination test [ 35 , 36 , 37 ].…”

“…In these vaccines, VACV acts as a vector capable of delivering antigens from other organisms [ 23 ]. While in many recombinant vaccines a viral antigen has been inserted, some of them have also been developed against bacteria [ 86 ] or protists [ 34 , 87 , 88 ]. These vaccines simulate infection by the pathogen from which the antigens are and elicit the immune response, by producing antigens for different pathogens.…”

Next generation vaccines and vectors: Designing downstream processes for recombinant protein‐based virus‐like particles

“…In addition, VLPs have been used as carrier systems for the presentation of foreign antigen epitopes to design new tailored vaccine candidates. Examples are the development of VLP‐based vaccine candidates against malaria [2, 3], diseases attributed to group A Streptococcus infections [4], Alzheimer's disease [5–7], asthma [8, 9], diabetes [10], tumor growth [11, 12], and the design of packaged VLPs for the delivery of anti‐cancer reagents [13]. Thus, VLP technology paves new ways for further medical applications such as immunotherapy of cancer, Alzheimer's disease, metabolic and chronic diseases [14].…”