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Sterile protection against malaria is independent of immune responses to the circumsporozoite protein.

Grüner AC, Mauduit M, Tewari R, Romero JF, Depinay N, Kayibanda M, Lallemand E, Chavatte JM, Crisanti A, Sinnis P, Mazier D, Corradin G, Snounou G, Rénia L - PLoS ONE (2007)

Bottom Line: Our data demonstrated that sterile immunity could be obtained despite the absence of immune responses specific to the CSP expressed by the parasite used for challenge.We conclude that other pre-erythrocytic parasite antigens, possibly hitherto uncharacterised, can be targeted to induce sterile immunity against malaria.From a broader perspective, our results raise the question as to whether immunodominant parasite antigens should be the favoured targets for vaccine development.

View Article: PubMed Central - PubMed

Affiliation: Institut Cochin, Department of Immunology, Université Paris Descartes, Centre National de Recherche Scientifique (CNRS) UMR 8104, Paris, France.

ABSTRACT

Background: Research aimed at developing vaccines against infectious diseases generally seeks to induce robust immune responses to immunodominant antigens. This approach has led to a number of efficient bacterial and viral vaccines, but it has yet to do so for parasitic pathogens. For malaria, a disease of global importance due to infection by Plasmodium protozoa, immunization with radiation-attenuated sporozoites uniquely leads to long lasting sterile immunity against infection. The circumsporozoite protein (CSP), an important component of the sporozoite's surface, remains the leading candidate antigen for vaccines targeting the parasite's pre-erythrocytic stages. Difficulties in developing CSP-based vaccines that reproduce the levels of protection afforded by radiation-attenuated sporozoites have led us to question the role of CSP in the acquisition of sterile immunity. We have used a parasite transgenic for the CSP because it allowed us to test whether a major immunodominant Plasmodium antigen is indeed needed for the induction of sterile protective immunity against infection.

Methodology/main findings: We employed a P. berghei parasite line that expresses a heterologous CSP from P. falciparum in order to assess the role of the CSP in the protection conferred by vaccination with radiation-attenuated P. berghei parasites. Our data demonstrated that sterile immunity could be obtained despite the absence of immune responses specific to the CSP expressed by the parasite used for challenge.

Conclusions: We conclude that other pre-erythrocytic parasite antigens, possibly hitherto uncharacterised, can be targeted to induce sterile immunity against malaria. From a broader perspective, our results raise the question as to whether immunodominant parasite antigens should be the favoured targets for vaccine development.

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Comparison of the amino acid sequences of the P. berghei ANKA clone cy17 (34) and P. falciparum Welcome strain (35) CSP polypeptides.Black dots represent identical amino acid residues while bars represent amino acid residues with similar characteristics. The repeat regions (including the pre- and post-repeat sequences) are underlined.
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pone-0001371-g001: Comparison of the amino acid sequences of the P. berghei ANKA clone cy17 (34) and P. falciparum Welcome strain (35) CSP polypeptides.Black dots represent identical amino acid residues while bars represent amino acid residues with similar characteristics. The repeat regions (including the pre- and post-repeat sequences) are underlined.

Mentions: Given the major differences between the sequences of the P. berghei and P. falciparum CSP genes (Figure 1), we predicted that the immune responses induced by immunisation with irradiated sporozoites of the wild type P. berghei will be specific to the P. berghei CSP. In this case, any protection observed in the immunised mice challenged with the P. berghei [PfCS] parasites, would be due to immune responses independent of CSP.


Sterile protection against malaria is independent of immune responses to the circumsporozoite protein.

Grüner AC, Mauduit M, Tewari R, Romero JF, Depinay N, Kayibanda M, Lallemand E, Chavatte JM, Crisanti A, Sinnis P, Mazier D, Corradin G, Snounou G, Rénia L - PLoS ONE (2007)

Comparison of the amino acid sequences of the P. berghei ANKA clone cy17 (34) and P. falciparum Welcome strain (35) CSP polypeptides.Black dots represent identical amino acid residues while bars represent amino acid residues with similar characteristics. The repeat regions (including the pre- and post-repeat sequences) are underlined.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2147056&req=5

pone-0001371-g001: Comparison of the amino acid sequences of the P. berghei ANKA clone cy17 (34) and P. falciparum Welcome strain (35) CSP polypeptides.Black dots represent identical amino acid residues while bars represent amino acid residues with similar characteristics. The repeat regions (including the pre- and post-repeat sequences) are underlined.
Mentions: Given the major differences between the sequences of the P. berghei and P. falciparum CSP genes (Figure 1), we predicted that the immune responses induced by immunisation with irradiated sporozoites of the wild type P. berghei will be specific to the P. berghei CSP. In this case, any protection observed in the immunised mice challenged with the P. berghei [PfCS] parasites, would be due to immune responses independent of CSP.

Bottom Line: Our data demonstrated that sterile immunity could be obtained despite the absence of immune responses specific to the CSP expressed by the parasite used for challenge.We conclude that other pre-erythrocytic parasite antigens, possibly hitherto uncharacterised, can be targeted to induce sterile immunity against malaria.From a broader perspective, our results raise the question as to whether immunodominant parasite antigens should be the favoured targets for vaccine development.

View Article: PubMed Central - PubMed

Affiliation: Institut Cochin, Department of Immunology, Université Paris Descartes, Centre National de Recherche Scientifique (CNRS) UMR 8104, Paris, France.

ABSTRACT

Background: Research aimed at developing vaccines against infectious diseases generally seeks to induce robust immune responses to immunodominant antigens. This approach has led to a number of efficient bacterial and viral vaccines, but it has yet to do so for parasitic pathogens. For malaria, a disease of global importance due to infection by Plasmodium protozoa, immunization with radiation-attenuated sporozoites uniquely leads to long lasting sterile immunity against infection. The circumsporozoite protein (CSP), an important component of the sporozoite's surface, remains the leading candidate antigen for vaccines targeting the parasite's pre-erythrocytic stages. Difficulties in developing CSP-based vaccines that reproduce the levels of protection afforded by radiation-attenuated sporozoites have led us to question the role of CSP in the acquisition of sterile immunity. We have used a parasite transgenic for the CSP because it allowed us to test whether a major immunodominant Plasmodium antigen is indeed needed for the induction of sterile protective immunity against infection.

Methodology/main findings: We employed a P. berghei parasite line that expresses a heterologous CSP from P. falciparum in order to assess the role of the CSP in the protection conferred by vaccination with radiation-attenuated P. berghei parasites. Our data demonstrated that sterile immunity could be obtained despite the absence of immune responses specific to the CSP expressed by the parasite used for challenge.

Conclusions: We conclude that other pre-erythrocytic parasite antigens, possibly hitherto uncharacterised, can be targeted to induce sterile immunity against malaria. From a broader perspective, our results raise the question as to whether immunodominant parasite antigens should be the favoured targets for vaccine development.

Show MeSH
Related in: MedlinePlus