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Plasmodium berghei circumsporozoite protein encapsulated in oligomannose-coated liposomes confers protection against sporozoite infection in mice.

Terkawi MA, Kuroda Y, Fukumoto S, Tanaka S, Kojima N, Nishikawa Y - Malar. J. (2014)

Bottom Line: The design and development of an effective malaria vaccine against the pre-erythrocytic and erythrocytic-stages of infection present a great challenge.The current results represent the use of an oligomannose-coated liposome-based vaccine against pre-erythrocytic and erythrocytic stages malaria infection.This approach may offer a new vaccination strategy against malaria infection.

View Article: PubMed Central - PubMed

Affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan. nisikawa@obihiro.ac.jp.

ABSTRACT

Background: The design and development of an effective malaria vaccine against the pre-erythrocytic and erythrocytic-stages of infection present a great challenge.

Methods: In the present study, protective efficacy of oligomannose-coated liposome (OML)-entrapped merozoite and sporozoite antigens against Plasmodium berghei challenge infection in BALB/c mice was evaluated.

Results: Subcutaneous immunization with truncated merozoite surface protein 1 entrapped with OML (OML-PbMSP1) prolonged survival, but failed to protect the mice from erythrocytic-stage infection, despite the antigen-specific antibody responses induced by the immunization regimen. In contrast, immunization with circumsporozoite protein entrapped with OML (OML-PbCSP) elicited antigen-specific humoral and cellular responses, which correlated with substantial protection against sporozoite challenge infections.

Conclusions: The current results represent the use of an oligomannose-coated liposome-based vaccine against pre-erythrocytic and erythrocytic stages malaria infection. This approach may offer a new vaccination strategy against malaria infection.

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Related in: MedlinePlus

Efficacy of immunization with OML-PbMSP1. ELISA detection of antigen-specific IgG1 (A) and IgG2a (B) in mice immunized with recombinant PbMSP1 over the course of immunization. The mean optical density (OD) was determined at a wavelength of 415 nm. Each bar represents the mean ± SD for used mice per group and results are representative of two independent experiments. Different superscript letters indicate statistically significant differences (P <0.05) among groups at each time-point as determined by a one-way analysis of variance followed by Tukey’s multiple comparison test. Parasitemias (C) and survival rates (D) after challenge infection with pRBCs. Each bar represents the mean ± SD for 11 mice per group (only 6 mice for PbMSP1) and results are from two pooled independent experiments. Mice were either immunized by OML-PbMSP1 (OML-PbMSP1), OML alone (OML-PBS), or naked PbMSP1 (PbMSP1), or not immunized (None).
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Fig2: Efficacy of immunization with OML-PbMSP1. ELISA detection of antigen-specific IgG1 (A) and IgG2a (B) in mice immunized with recombinant PbMSP1 over the course of immunization. The mean optical density (OD) was determined at a wavelength of 415 nm. Each bar represents the mean ± SD for used mice per group and results are representative of two independent experiments. Different superscript letters indicate statistically significant differences (P <0.05) among groups at each time-point as determined by a one-way analysis of variance followed by Tukey’s multiple comparison test. Parasitemias (C) and survival rates (D) after challenge infection with pRBCs. Each bar represents the mean ± SD for 11 mice per group (only 6 mice for PbMSP1) and results are from two pooled independent experiments. Mice were either immunized by OML-PbMSP1 (OML-PbMSP1), OML alone (OML-PBS), or naked PbMSP1 (PbMSP1), or not immunized (None).

Mentions: To evaluate the immunogenicity of the OML-PbMSP1 immunization, sera were serially sampled prior to and after each immunization, and the antibody responses were examined by ELISA using PbMSP1. Of note, OML-PbMSP1 induced highly specific antibody responses in the mice consisting of IgG1 and IgG2a isotypes (Figure 2A,B). Indeed, the PbMSP1-specific antibodies induced by immunization with OML-PbMSP1 were significantly greater than those induced by naked antigen over the course of the immunizations, and it was found that the titers increased at least 10-fold after the third immunization (Table 1 and Figure 2A,B). No PbMSP1-specific antibody responses were detected in mice that received OML or no immunization. Thereafter, to evaluate the protective efficacy of OML-PbMSP1 against erythrocytic-stage infection, mice were infected with pRBCs and their parasitemia and survival rates were monitored over a 30-day period. Mice showed a patent parasitemia by day 3 post-infection and succumbed to malaria infection within one month (Figure 2C,D). Notably, the OML-PbMSP1-immunized mice had a delay in their onset of parasitemia (36.4%, 4/11 mice) and prolonged survival as compared with the other groups of mice (Table 1).Figure 2


Plasmodium berghei circumsporozoite protein encapsulated in oligomannose-coated liposomes confers protection against sporozoite infection in mice.

Terkawi MA, Kuroda Y, Fukumoto S, Tanaka S, Kojima N, Nishikawa Y - Malar. J. (2014)

Efficacy of immunization with OML-PbMSP1. ELISA detection of antigen-specific IgG1 (A) and IgG2a (B) in mice immunized with recombinant PbMSP1 over the course of immunization. The mean optical density (OD) was determined at a wavelength of 415 nm. Each bar represents the mean ± SD for used mice per group and results are representative of two independent experiments. Different superscript letters indicate statistically significant differences (P <0.05) among groups at each time-point as determined by a one-way analysis of variance followed by Tukey’s multiple comparison test. Parasitemias (C) and survival rates (D) after challenge infection with pRBCs. Each bar represents the mean ± SD for 11 mice per group (only 6 mice for PbMSP1) and results are from two pooled independent experiments. Mice were either immunized by OML-PbMSP1 (OML-PbMSP1), OML alone (OML-PBS), or naked PbMSP1 (PbMSP1), or not immunized (None).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4232614&req=5

Fig2: Efficacy of immunization with OML-PbMSP1. ELISA detection of antigen-specific IgG1 (A) and IgG2a (B) in mice immunized with recombinant PbMSP1 over the course of immunization. The mean optical density (OD) was determined at a wavelength of 415 nm. Each bar represents the mean ± SD for used mice per group and results are representative of two independent experiments. Different superscript letters indicate statistically significant differences (P <0.05) among groups at each time-point as determined by a one-way analysis of variance followed by Tukey’s multiple comparison test. Parasitemias (C) and survival rates (D) after challenge infection with pRBCs. Each bar represents the mean ± SD for 11 mice per group (only 6 mice for PbMSP1) and results are from two pooled independent experiments. Mice were either immunized by OML-PbMSP1 (OML-PbMSP1), OML alone (OML-PBS), or naked PbMSP1 (PbMSP1), or not immunized (None).
Mentions: To evaluate the immunogenicity of the OML-PbMSP1 immunization, sera were serially sampled prior to and after each immunization, and the antibody responses were examined by ELISA using PbMSP1. Of note, OML-PbMSP1 induced highly specific antibody responses in the mice consisting of IgG1 and IgG2a isotypes (Figure 2A,B). Indeed, the PbMSP1-specific antibodies induced by immunization with OML-PbMSP1 were significantly greater than those induced by naked antigen over the course of the immunizations, and it was found that the titers increased at least 10-fold after the third immunization (Table 1 and Figure 2A,B). No PbMSP1-specific antibody responses were detected in mice that received OML or no immunization. Thereafter, to evaluate the protective efficacy of OML-PbMSP1 against erythrocytic-stage infection, mice were infected with pRBCs and their parasitemia and survival rates were monitored over a 30-day period. Mice showed a patent parasitemia by day 3 post-infection and succumbed to malaria infection within one month (Figure 2C,D). Notably, the OML-PbMSP1-immunized mice had a delay in their onset of parasitemia (36.4%, 4/11 mice) and prolonged survival as compared with the other groups of mice (Table 1).Figure 2

Bottom Line: The design and development of an effective malaria vaccine against the pre-erythrocytic and erythrocytic-stages of infection present a great challenge.The current results represent the use of an oligomannose-coated liposome-based vaccine against pre-erythrocytic and erythrocytic stages malaria infection.This approach may offer a new vaccination strategy against malaria infection.

View Article: PubMed Central - PubMed

Affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan. nisikawa@obihiro.ac.jp.

ABSTRACT

Background: The design and development of an effective malaria vaccine against the pre-erythrocytic and erythrocytic-stages of infection present a great challenge.

Methods: In the present study, protective efficacy of oligomannose-coated liposome (OML)-entrapped merozoite and sporozoite antigens against Plasmodium berghei challenge infection in BALB/c mice was evaluated.

Results: Subcutaneous immunization with truncated merozoite surface protein 1 entrapped with OML (OML-PbMSP1) prolonged survival, but failed to protect the mice from erythrocytic-stage infection, despite the antigen-specific antibody responses induced by the immunization regimen. In contrast, immunization with circumsporozoite protein entrapped with OML (OML-PbCSP) elicited antigen-specific humoral and cellular responses, which correlated with substantial protection against sporozoite challenge infections.

Conclusions: The current results represent the use of an oligomannose-coated liposome-based vaccine against pre-erythrocytic and erythrocytic stages malaria infection. This approach may offer a new vaccination strategy against malaria infection.

Show MeSH
Related in: MedlinePlus