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

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.

SUBMITTER: Terkawi MA

PROVIDER: S-EPMC4232614 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Terkawi Mohamad Alaa MA Kuroda Yasuhiro Y Fukumoto Shinya S Tanaka Sachi S Kojima Naoya N Nishikawa Yoshifumi Y

Malaria journal 20141105

<h4>Background</h4>The design and development of an effective malaria vaccine against the pre-erythrocytic and erythrocytic-stages of infection present a great challenge.<h4>Methods</h4>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.<h4>Results</h4>Subcutaneous immunization with truncated merozoite surface protein 1 entrapped with OML (OML-PbMSP ...[more]

PMID: 25373617

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Project description:Malaria-causing Plasmodium parasites have a complex life cycle and present numerous antigen targets that may contribute to protective immune responses. The currently recommended vaccine-RTS,S-functions by targeting the Plasmodium falciparum circumsporozoite protein (CSP), which is the most abundant surface protein of the sporozoite form responsible for initiating infection of the human host. Despite showing only moderate efficacy, RTS,S has established a strong foundation for the development of next-generation subunit vaccines. Our previous work characterizing the sporozoite surface proteome identified additional non-CSP antigens that may be useful as immunogens individually or in combination with CSP. In this study, we examined eight such antigens using the rodent malaria parasite Plasmodium yoelii as a model system. We demonstrate that despite conferring weak protection individually, coimmunizing each of several of these antigens alongside CSP could significantly enhance the sterile protection achieved by CSP immunization alone. Thus, our work provides compelling evidence that a multiantigen preerythrocytic vaccine approach may enhance protection compared to CSP-only vaccines. This lays the groundwork for further studies aimed at testing the identified antigen combinations in human vaccination trials that assess efficacy with controlled human malaria infection. IMPORTANCE The currently approved malaria vaccine targets a single parasite protein (CSP) and results in only partial protection. We tested several additional vaccine targets in combination with CSP to identify those that could enhance protection from infection upon challenge in the mouse malaria model. In identifying several such enhancing vaccine targets, our work indicates that a multiprotein immunization approach may be a promising avenue to achieving higher levels of protection from infection. Our work identified several candidate leads for follow-up in the models relevant for human malaria and provides an experimental framework for efficiently carrying out such screens for other combinations of vaccine targets.

Dataset Information

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

Publications

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

Similar Datasets

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