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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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Related in: MedlinePlus

Sterile protection in mice immunized with P. berghei irradiated sporozoites and challenged with P. berghei or P. berghei [PfCS] sporozoites.Mice were immunized with 1 or 3 injections of P. berghei (indicated on the left of the panel) before challenge with 5 000 P. berghei or P. berghei [PfCS] sporozoites. All naive control mice developed a patent blood-stage infection. The data are representative of those obtained in duplicate experiments.
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pone-0001371-g004: Sterile protection in mice immunized with P. berghei irradiated sporozoites and challenged with P. berghei or P. berghei [PfCS] sporozoites.Mice were immunized with 1 or 3 injections of P. berghei (indicated on the left of the panel) before challenge with 5 000 P. berghei or P. berghei [PfCS] sporozoites. All naive control mice developed a patent blood-stage infection. The data are representative of those obtained in duplicate experiments.

Mentions: Since minimal CSP cross-reactive responses are induced by immunisation with wild type P. berghei irradiated sporozoites, if the sterile protection induced were dependent on CSP-specific immune responses, then the immunized mice should not be protected against challenge with P. berghei [PfCS] sporozoites that express a heterologous CSP. However, BALB/c mice immunized, either once or three times, with P. berghei irradiated sporozoites were found to be protected from infection whether challenged with homologous sporozoites or with those from P. berghei [PfCS] (Figure 4). These observations were not restricted to BALB/c mice since [BALB/c×C57BL/6] F1 mice immunized three times with P. berghei irradiated sporozoites and challenged with P. berghei [PfCS] were also protected (Figure 5). These results demonstrate that the acquisition of sterile immunity can be achieved independently of the CSP-specific cellular and humoral responses induced by immunization. Thus, it can be concluded that the contribution of CSP is not essential to sterile protection.


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)

Sterile protection in mice immunized with P. berghei irradiated sporozoites and challenged with P. berghei or P. berghei [PfCS] sporozoites.Mice were immunized with 1 or 3 injections of P. berghei (indicated on the left of the panel) before challenge with 5 000 P. berghei or P. berghei [PfCS] sporozoites. All naive control mice developed a patent blood-stage infection. The data are representative of those obtained in duplicate experiments.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0001371-g004: Sterile protection in mice immunized with P. berghei irradiated sporozoites and challenged with P. berghei or P. berghei [PfCS] sporozoites.Mice were immunized with 1 or 3 injections of P. berghei (indicated on the left of the panel) before challenge with 5 000 P. berghei or P. berghei [PfCS] sporozoites. All naive control mice developed a patent blood-stage infection. The data are representative of those obtained in duplicate experiments.
Mentions: Since minimal CSP cross-reactive responses are induced by immunisation with wild type P. berghei irradiated sporozoites, if the sterile protection induced were dependent on CSP-specific immune responses, then the immunized mice should not be protected against challenge with P. berghei [PfCS] sporozoites that express a heterologous CSP. However, BALB/c mice immunized, either once or three times, with P. berghei irradiated sporozoites were found to be protected from infection whether challenged with homologous sporozoites or with those from P. berghei [PfCS] (Figure 4). These observations were not restricted to BALB/c mice since [BALB/c×C57BL/6] F1 mice immunized three times with P. berghei irradiated sporozoites and challenged with P. berghei [PfCS] were also protected (Figure 5). These results demonstrate that the acquisition of sterile immunity can be achieved independently of the CSP-specific cellular and humoral responses induced by immunization. Thus, it can be concluded that the contribution of CSP is not essential to sterile protection.

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