Jacquelynne Cervantes

Characterization of S3Pvac Anti-Cysticercosis Vaccine Components: Implications for the Development of an Anti-Cestodiasis Vaccine

Background Cysticercosis and hydatidosis seriously affect human health and are responsible for considerable economic loss in animal husbandry in non-developed and developed countries. S3Pvac and EG95 are the only field trial-tested vaccine candidates against cysticercosis and hydatidosis, respectively. S3Pvac is composed of three peptides (KETc1, GK1 and KETc12), originally identified in a Taenia crassiceps cDNA library. S3Pvac synthetically and recombinantly expressed is effective against experimentally and naturally acquired cysticercosis. Methodology/Principal Findings In this study, the homologous sequences of two of the S3Pvac peptides, GK1 and KETc1, were identified and further characterized in Taenia crassiceps WFU, Taenia solium, Taenia saginata, Echinococcus granulosus and Echinococcus multilocularis. Comparisons of the nucleotide and amino acid sequences coding for KETc1 and GK1 revealed significant homologies in these species. The predicted secondary structure of GK1 is almost identical between the species, while some differences were observed in the C terminal region of KETc1 according to 3D modeling. A KETc1 variant with a deletion of three C-terminal amino acids protected to the same extent against experimental murine cysticercosis as the entire peptide. On the contrary, immunization with the truncated GK1 failed to induce protection. Immunolocalization studies revealed the non stage-specificity of the two S3Pvac epitopes and their persistence in the larval tegument of all species and in Taenia adult tapeworms. Conclusions/Significance These results indicate that GK1 and KETc1 may be considered candidates to be included in the formulation of a multivalent and multistage vaccine against these cestodiases because of their enhancing effects on other available vaccine candidates.

Transgenic plants: a 5-year update on oral antipathogen vaccine development

The progressive interest in transgenic plants as advantageous platforms for the production and oral delivery of vaccines has led to extensive research and improvements in this technology over recent years. In this paper, the authors examine the most significant advances in this area, including novel approaches for higher yields and better containment, and the continued evaluation of new vaccine prototypes against several infectious diseases. The use of plants to deliver vaccine candidates against viruses, bacteria, and eukaryotic parasites within the last 5 years is discussed, focusing on innovative expression strategies and the immunogenic potential of new vaccines. A brief section on the state of the art in mucosal immunity is also included.

Development of the S3Pvac Vaccine Against Porcine Taenia solium Cysticercosis: A Historical Review

Abstract:  Herein we present a review of our research dealing with vaccination against experimental and naturally acquired porcine Taenia solium cysticercosis using Taenia crassiceps-derived antigens. Results strongly support that the different versions of S3Pvac vaccine are indeed effective against porcine T. solium cysticercosis. Immunological results related to vaccination prove that protection is at least partially mediated by specific immunity. The data also support the validity of T. crassiceps murine cysticercosis as an effective tool to identify vaccine candidates against some metacestode infections.

Recombinant S3Pvac-phage anticysticercosis vaccine: Simultaneous protection against cysticercosis and hydatid disease in rural pigs

This paper provides macroscopic and histological evidence on the statistically significant protective effects of S3Pvac-phage vaccination against porcine cysticercosis and hydatidosis. The study included 391 rustically bred pigs (187 vaccinated and 204 controls). Vaccination significantly reduced the prevalence of cysticercosis by 61.7%. Vaccination also significantly reduced by 56.1% the prevalence of hydatidosis caused by Echinococcus granulosus in pigs. The presence of the vaccine epitopes in both cestodes is probably involved in the cross-protection observed. Increased inflammation was found in 5% of cysticerci recovered from controls, versus 24% from vaccinated pigs (P<0.01). Hydatid cysts were non-inflammatory in either group. Vaccination was effective to prevent one single disease, but it failed to prevent the simultaneous infections with both parasites in a same pig. The widening of the S3Pvac-phage vaccine protective repertoire to include hydatidosis is a convenient feature that should reduce the prevalence of two frequent zoonoses that affect rustic porcine breading with a single action. Thus, the costs of two different vaccination programs would be reduced to a single one with significant reduction in both zoonoses.

Heterologous Prime-Boost Oral Immunization with GK-1 Peptide from Taenia crassiceps Cysticerci Induces Protective Immunity

ABSTRACT Oral immunization is a goal in vaccine development, particularly for pathogens that enter the host through the mucosal system. This study was designed to explore the immunogenic properties of the Taenia crassiceps protective peptide GK-1 administered orally. Mice were orally immunized with the synthetic GK-1 peptide in its linear form with or without the Brucella lumazine synthase (BLS) protein adjuvant or as a chimera recombinantly bound to BLS (BLS-GK-1). Mice were boosted twice with GK-1 only at 15-day intervals. A significant rate of protection of 64.7% was achieved in GK-1-immunized mice, and that rate significantly increased to 91.8 and 96% when mice were primed with GK-1 coadministered with BLS as an adjuvant and BLS as a carrier, respectively. Specific antibodies and T cell activation and proliferation accompanied the protection induced, revealing the potent immunogenicity of GK-1. Through immunohistochemical studies, GK-1 was detected in T and B cell zones of the Peyers patches (PP) and mesenteric lymph nodes. In the latter, abundant proliferating cells were detected by 5′-bromo-2′-deoxyuridine incorporation. No proliferation was detected in PP. Altogether, these results portray the potent immunogenic properties of GK-1 administered orally and reinforce the usefulness of BLS as an adjuvant and adequate vaccine delivery system for oral vaccines.

RENEWED HOPE FOR A VACCINE AGAINST THE INTESTINAL ADULT TAENIA SOLIUM

Review of experimental and observational evidence about various cestode infections of mammalian hosts revives hope for the development of an effective vaccine against adult intestinal tapeworms, the central protagonists in their transmission dynamics. As for Taenia solium, there are abundant immunological data regarding cysticercosis in humans and pigs, but information about human taeniasis is scarce. A single publication reporting protection against T. solium taeniasis by experimental primo infection and by vaccination of an experimental foster host, the immunocompetent female hamster, kindles the hope of a vaccine against the tapeworm to be used in humans, its only natural definitive host.

Development of the S3Pvac Vaccine Against Murine Taenia crassiceps Cysticercosis: A Historical Review

Abstract:  Our work of the last 25 yr was concerned with the development of a vaccine aimed to prevent porcine Taenia solium cysticercosis and was based on cross-reacting Taenia crassiceps antigens that had proved protective against experimental intraperitoneal murine T. crassiceps cysticercosis (EIMTcC). In recent times the efficacy of the vaccine has been considered in need of confirmation, and the use of EIMTcC has been questioned as a valid tool in screening for vaccine candidates among the many antigens possibly involved. A review of our work divided in 2 parts is presented at this point, the first dealing with EIMTcC and the second with porcine T. solium cysticercosis (presented in this issue). Herein, we revise our results using EIMTcC as a measure of the protective capacity of T. crassiceps complex antigen mixtures, of purified native antigens, and of S3Pvac anti-cysticercosis vaccine composed by 3 protective peptides: GK-1, KETc1, and KETc12 either synthetic or recombinantly expressed and collectively or separately, by diverse delivery systems when administered at different doses and by different routes. Statistical analyses of the data lead confidently to the strong inference that S3Pvac is indeed an effective vaccine against EIMTcC via specific and non-specific mechanisms of protection.

Influenza vaccine: development of a novel intranasal and subcutaneous recombinant adjuvant.

The synthetic peptide GK-1, derived from Taenia crassiceps, enhances the protection induced by human influenza vaccine in both young and aged mice. Herein, the adjuvant properties of GK-1 fused to the pVIII protein of a heat-inactivated phagemid vector (FGK1) when co-administered with the influenza vaccine were assessed, to evaluate its feasibility as a low-cost adjuvant. In mice, FGK1 significantly increased the expected IgG and IgA anti-influenza antibody levels both in sera and in bronchoalveolar fluids when intranasally or subcutaneously co-administered with influenza vaccine. Single-dose pig co-immunization with FGK1 and influenza vaccine induced serum levels of IgG anti-influenza antibodies similar to those elicited by a two-dose immunization with the influenza vaccine alone. Preclinical evaluation of FGK1 with the influenza vaccine is currently in progress, in order to recommend its use for veterinary purposes.