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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

Humoral responses in mice to immunization with OML-PbCSP. ELISA detection of antigen-specific IgG1 (A) and IgG2a (B) in mice immunized with recombinant PbCSP. 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. Mice were either immunized by OML-PbCSP (OML-PbCSP), OML alone (OML-PBS), naked PbCSP (PbCSP) or not immunized (None). Different superscript letters indicate statistically significant differences (P <0.05) among groups as determined by a one-way analysis of variance followed by Tukey’s multiple comparison test.
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Fig3: Humoral responses in mice to immunization with OML-PbCSP. ELISA detection of antigen-specific IgG1 (A) and IgG2a (B) in mice immunized with recombinant PbCSP. 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. Mice were either immunized by OML-PbCSP (OML-PbCSP), OML alone (OML-PBS), naked PbCSP (PbCSP) or not immunized (None). Different superscript letters indicate statistically significant differences (P <0.05) among groups as determined by a one-way analysis of variance followed by Tukey’s multiple comparison test.

Mentions: The immunization regimen with either OML-PbCSP (3 μg) induced strong and specific antibody responses to the antigen, which consisted of IgG1 and IgG2a isotypes (Figure 3A-B). Antigen-specific IgG1 and IgG2a were significantly greater in mice immunized with OML-PbCSP than in mice immunized with the corresponding naked antigen over the course of the immunizations (Figure 3A-B). No specific-PbCSP antibody responses were observed in mice that received OML or no immunization. Consistently, antibody titration against antigen revealed that the IgG1 and IgG2a titers increased at least 20-fold and 16-fold, respectively, in the OML-based antigen-immunized mice as compared with those that received the corresponding naked antigen (Table 2). These results showed that the immunization regimen for OML-PbCSP was capable of inducing robust humoral responses consisting of IgG1 and IgG2a isotypes. Next, immunized mice were infected s.c. with a live inoculum of 2 × 103 sporozoites/mouse 14 days after their last boost, after which their parasitemia and survival rates were monitored over a 30-day period. Notably, 54% of the OML-PbCSP-immunized mice showed complete sterile protection, as defined by the absence of patent parasitemia over the study period. In contrast, the OML-immunized control group showed 9.1% protection (Table 2). No protection was observed in the mice that received the naked antigen immunization regimen or no immunization (Table 2). Moreover, comparison of the parasitemia curves revealed that the OML-antigen-immunized mice, which had pRBCs, experienced at least a 1-day delay in the onset of parasitemia as compared with mice immunized with naked antigen or OML alone, or those that were not immunized (Table 2). Moreover, antibody titer of anti-PbCSP-specific IgG2a in protected mice by OML-PbCSP immunization tended to be higher than those in susceptible mice received same immunization (protected; 3520 ± 787, unprotected; 1733 ± 1753, P = 0.0504), while there was no significant difference in the antibody titer of the specific IgG1. Furthermore, use of a modified immunization regimen comprising OML-PbCSP with a single boost resulted in a reduced protection rate as noted as 16.7% (Table 2). The immunization regimen of OML-PbCSP containing 1 μg antigen with two boots resulted in 66.7% complete protection in mice. Nonetheless, lower protection correlated with reduced antibody responses was observed in OML-PbCSP-immunized mice with single boost (Table 2). These results show that the immunization regimen with OML-PbCSP conferred a significant degree of protection against pre-erythrocytic stage infection of P. berghei in the BALB/c mice.Figure 3


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)

Humoral responses in mice to immunization with OML-PbCSP. ELISA detection of antigen-specific IgG1 (A) and IgG2a (B) in mice immunized with recombinant PbCSP. 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. Mice were either immunized by OML-PbCSP (OML-PbCSP), OML alone (OML-PBS), naked PbCSP (PbCSP) or not immunized (None). Different superscript letters indicate statistically significant differences (P <0.05) among groups as determined by a one-way analysis of variance followed by Tukey’s multiple comparison test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Humoral responses in mice to immunization with OML-PbCSP. ELISA detection of antigen-specific IgG1 (A) and IgG2a (B) in mice immunized with recombinant PbCSP. 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. Mice were either immunized by OML-PbCSP (OML-PbCSP), OML alone (OML-PBS), naked PbCSP (PbCSP) or not immunized (None). Different superscript letters indicate statistically significant differences (P <0.05) among groups as determined by a one-way analysis of variance followed by Tukey’s multiple comparison test.
Mentions: The immunization regimen with either OML-PbCSP (3 μg) induced strong and specific antibody responses to the antigen, which consisted of IgG1 and IgG2a isotypes (Figure 3A-B). Antigen-specific IgG1 and IgG2a were significantly greater in mice immunized with OML-PbCSP than in mice immunized with the corresponding naked antigen over the course of the immunizations (Figure 3A-B). No specific-PbCSP antibody responses were observed in mice that received OML or no immunization. Consistently, antibody titration against antigen revealed that the IgG1 and IgG2a titers increased at least 20-fold and 16-fold, respectively, in the OML-based antigen-immunized mice as compared with those that received the corresponding naked antigen (Table 2). These results showed that the immunization regimen for OML-PbCSP was capable of inducing robust humoral responses consisting of IgG1 and IgG2a isotypes. Next, immunized mice were infected s.c. with a live inoculum of 2 × 103 sporozoites/mouse 14 days after their last boost, after which their parasitemia and survival rates were monitored over a 30-day period. Notably, 54% of the OML-PbCSP-immunized mice showed complete sterile protection, as defined by the absence of patent parasitemia over the study period. In contrast, the OML-immunized control group showed 9.1% protection (Table 2). No protection was observed in the mice that received the naked antigen immunization regimen or no immunization (Table 2). Moreover, comparison of the parasitemia curves revealed that the OML-antigen-immunized mice, which had pRBCs, experienced at least a 1-day delay in the onset of parasitemia as compared with mice immunized with naked antigen or OML alone, or those that were not immunized (Table 2). Moreover, antibody titer of anti-PbCSP-specific IgG2a in protected mice by OML-PbCSP immunization tended to be higher than those in susceptible mice received same immunization (protected; 3520 ± 787, unprotected; 1733 ± 1753, P = 0.0504), while there was no significant difference in the antibody titer of the specific IgG1. Furthermore, use of a modified immunization regimen comprising OML-PbCSP with a single boost resulted in a reduced protection rate as noted as 16.7% (Table 2). The immunization regimen of OML-PbCSP containing 1 μg antigen with two boots resulted in 66.7% complete protection in mice. Nonetheless, lower protection correlated with reduced antibody responses was observed in OML-PbCSP-immunized mice with single boost (Table 2). These results show that the immunization regimen with OML-PbCSP conferred a significant degree of protection against pre-erythrocytic stage infection of P. berghei in the BALB/c mice.Figure 3

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