Immunogenicity of a Prime-Boost Vaccine Containing the Circumsporozoite Proteins of Plasmodium vivax in Rodents

Teixeira, Laís Helena; Tararam, Cibele Aparecida; Lásaro, Marcio O.; Camacho, Ariane Guglielmi Ariza; Ersching, Jonatan; Leal, Monica T.; Herrera, Sócrates; Bruna-Romero, Oscar; Soares, Irene S.; Nussenzweig, Ruth S.; Ertl, Hildegund C. J.; Nussenzweig, Victor; Rodrigues, Maurício M.

doi:10.1128/iai.01410-13

Cited by 31 publications

(60 citation statements)

References 58 publications

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“…Finally, these preliminary GIS-based epidemiological maps for malaria will also be useful in the future when planning for the development of trials with vaccine candidates, which are also under development today, not only for P. falciparum but also P. vivax malaria in Latin America and in Colombia [42][43][44].…”

Section: Discussionmentioning

confidence: 99%

Mapping malaria in municipalities of the Coffee Triangle region of Colombia using Geographic Information Systems (GIS)

Rodríguez‐Morales

Orrego-Acevedo

Zambrano-Muñoz

et al. 2015

Journal of Infection and Public Health

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Geographical Information Systems (GIS) have been used extensively for the development of epidemiological maps of malaria but not in the Coffee Triangle region of Colombia, endemic for P. vivax, P. falciparum and P. malariae. Surveillance case data (2007-2011) were used to estimate annual incidence rates per Plasmodium spp. (cases/100,000 pop) to develop the first malaria maps in the 53 municipalities of this region (departments Caldas, Quindío, Risaralda). The GIS software used was Kosmo Desktop 3.0RC1(®). Thirty thematic maps were developed according to the municipalities, years, parasite etiology, and uncomplicated and complicated cases. A total of 6582 cases were reported (6478 uncomplicated and 104 complicated, 77.8% Risaralda), for a cumulated rate of 269.46 cases/100,000 pop. Among uncomplicated cases, 5722 corresponded to P. vivax (234.25 cases/100,000 pop), 475 to P. falciparum (19.45 cases/100,000 pop), 8 to P. malariae (0.33 cases/100,000 pop) and 273 mixed (P. falciparum/P. vivax) (11.18 cases/100,000 pop). The highest rate reported was in the more undeveloped and rural municipality of Risaralda (Pueblo Rico, 57.7 cases/1000 pop, 2009). The burden of disease was concentrated in one department (>75% of the region). The use of GIS-based epidemiological maps helps to guide decision-making for the prevention and control of this public health problem that still represents a significant issue in the region and the country, particularly in children.

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Section: Discussionmentioning

confidence: 99%

Mapping malaria in municipalities of the Coffee Triangle region of Colombia using Geographic Information Systems (GIS)

Rodríguez‐Morales

Orrego-Acevedo

Zambrano-Muñoz

et al. 2015

Journal of Infection and Public Health

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“…It is known that both humoral immunity and cellular immunity to the pre-erythrocytic parasite stages can provide protection against sporozoite infection (33). In the case of PvCSP, however, there is no cytotoxic T lymphocyte (CTL) epitope on the PvCSP sequence capable of recognition by C57BL/6 (H-2K b ) mice (34). Similarly, the BALB/c (H-2K d ) mice we used here may not be able to recognize the CTL epitope on PvCSP.…”

Section: Discussionmentioning

confidence: 99%

Baculovirus-Vectored Multistage Plasmodium vivax Vaccine Induces Both Protective and Transmission-Blocking Immunities against Transgenic Rodent Malaria Parasites

et al. 2014

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A multistage malaria vaccine targeting the pre-erythrocytic and sexual stages of Plasmodium could effectively protect individuals against infection from mosquito bites and provide transmission-blocking (TB) activity against the sexual stages of the parasite, respectively. This strategy could help prevent malaria infections in individuals and, on a larger scale, prevent malaria transmission in communities of endemicity. Here, we describe the development of a multistage Plasmodium vivax vaccine which simultaneously expresses P. vivax circumsporozoite protein (PvCSP) and P25 (Pvs25) protein of this species as a fusion protein, thereby acting as a pre-erythrocytic vaccine and a TB vaccine, respectively. A new-concept vaccine platform based on the baculovirus dual-expression system (BDES) was evaluated. The BDES-Pvs25-PvCSP vaccine displayed correct folding of the Pvs25-PvCSP fusion protein on the viral envelope and was highly expressed upon transduction of mammalian cells in vitro. This vaccine induced high levels of antibodies to Pvs25 and PvCSP and elicited protective (43%) and TB (82%) efficacies against transgenic P. berghei parasites expressing the corresponding P. vivax antigens in mice. Our data indicate that our BDES, which functions as both a subunit and DNA vaccine, can offer a promising multistage vaccine capable of delivering a potent antimalarial pre-erythrocytic and TB response via a single immunization regimen. Plasmodium vivax is currently the most widely distributed human malaria parasite, with an "at risk" population in 2010 of almost 3 billion people (a third of the global population) and approximately 100 to 300 million clinical cases each year (1, 2). Several factors, including (i) the recent appearance of chloroquine-resistant P. vivax, (ii) the lack of alternatives to primaquine for attacking the dormant liver-stage hypnozoites, and (iii) increasing global temperatures caused by climate change, raise concerns about increases in the risk of severe P. vivax disease (3-6). Although the importance of P. vivax vaccines is recognized, the lack of long-term in vitro culture systems in red blood cells and suitable animal models as well as the complex life cycle of this parasite has hindered advances in the development of a potent vaccine (7,8).The development of malaria vaccines has been focused mostly on single antigens from different stages of the parasite life cycle: (i) the pre-erythrocytic stages (including the liver stages), (ii) the asexual blood stages, and (iii) the mosquito sexual stages, where antigens expressed on the gametocyte, gamete, zygote, or ookinete are targeted to prevent transmission from the human hosts to the mosquito vectors (9). There are concerns that the single-stage vaccine may not be effective because of sequence variability among different parasite isolates, host genetic restriction of immune responses to specific epitopes, and short-lived protective immunity induced by some single-antigen vaccines (10). Therefore, a multistage vaccine, which targets several antigens exp...

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“…Most P. vivax antigens considered to have vaccine potential have been tested in in vitro studies as well as in preliminary preclinical studies in mice and primates [9][10][11][12][13]. Only a few of these antigens further selected by classical immuno-serological methods have undergone phase I clinical trials [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Plasmodium vivax Antigen Discovery Based on Alpha-Helical Coiled Coil Protein Motif

et al. 2014

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Protein α-helical coiled coil structures that elicit antibody responses, which block critical functions of medically important microorganisms, represent a means for vaccine development. By using bioinformatics algorithms, a total of 50 antigens with α-helical coiled coil motifs orthologous to Plasmodium falciparum were identified in the P. vivax genome. The peptides identified in silico were chemically synthesized; circular dichroism studies indicated partial or high α-helical content. Antigenicity was evaluated using human sera samples from malaria-endemic areas of Colombia and Papua New Guinea. Eight of these fragments were selected and used to assess immunogenicity in BALB/c mice. ELISA assays indicated strong reactivity of serum samples from individuals residing in malaria-endemic regions and sera of immunized mice, with the α-helical coiled coil structures. In addition, ex vivo production of IFN-γ by murine mononuclear cells confirmed the immunogenicity of these structures and the presence of T-cell epitopes in the peptide sequences. Moreover, sera of mice immunized with four of the eight antigens recognized native proteins on blood-stage P. vivax parasites, and antigenic cross-reactivity with three of the peptides was observed when reacted with both the P. falciparum orthologous fragments and whole parasites. Results here point to the α-helical coiled coil peptides as possible P. vivax malaria vaccine candidates as were observed for P. falciparum. Fragments selected here warrant further study in humans and non-human primate models to assess their protective efficacy as single components or assembled as hybrid linear epitopes.

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Immunogenicity of a Prime-Boost Vaccine Containing the Circumsporozoite Proteins of Plasmodium vivax in Rodents

Cited by 31 publications

References 58 publications

Mapping malaria in municipalities of the Coffee Triangle region of Colombia using Geographic Information Systems (GIS)

Mapping malaria in municipalities of the Coffee Triangle region of Colombia using Geographic Information Systems (GIS)

Baculovirus-Vectored Multistage Plasmodium vivax Vaccine Induces Both Protective and Transmission-Blocking Immunities against Transgenic Rodent Malaria Parasites

Plasmodium vivax Antigen Discovery Based on Alpha-Helical Coiled Coil Protein Motif

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