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Antigen export during liver infection of the malaria parasite augments protective immunity.

Montagna GN, Beigier-Bompadre M, Becker M, Kroczek RA, Kaufmann SH, Matuschewski K - MBio (2014)

Bottom Line: A fundamental question is whether recognition by effector CD8(+) T cells is restricted to sporozoite surface antigens or extends to parasite proteins that are synthesized during the extensive parasite expansion phase in the liver.Using a surrogate model antigen, we found that a cytoplasmic antigen is able to induce robust protective CD8(+) T-cell responses, but protein export further enhances immunogenicity and protection.Our results show that a cytoplasmic localization does not exclude a protein's candidacy for malaria subunit vaccines and that protein secretion can enhance protective immunity.

View Article: PubMed Central - PubMed

Affiliation: Parasitology Unit, Max Planck Institute for Infection Biology, Berlin, Germany montagnageo@gmail.com.

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Immunization with expOVA sporozoites enhances protection against reinfection. (A) Quantification of parasite liver loads in immunized mice that received OT-1 or OT-2 cells. C57BL/6 mice received 2 × 105 OT-I (CD8) T cells (OT-1) or OT-II (CD4) T cells (OT-2). Next, mice were immunized once with 10,000 irradiated WT (black), expOVA (red), or OVA (green) sporozoites. Control mice were immunized once without prior T-cell transfer. Twelve days after the last immunization, animals were challenged by i.v. injection of 10,000 sporozoites of the corresponding genotype. After 42 h, livers were removed and parasite loads were quantified by real-time PCR. Bars and whiskers show means ± standard deviations. *, P < 0.05; **, P < 0.01 (Mann-Whitney test).
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fig5: Immunization with expOVA sporozoites enhances protection against reinfection. (A) Quantification of parasite liver loads in immunized mice that received OT-1 or OT-2 cells. C57BL/6 mice received 2 × 105 OT-I (CD8) T cells (OT-1) or OT-II (CD4) T cells (OT-2). Next, mice were immunized once with 10,000 irradiated WT (black), expOVA (red), or OVA (green) sporozoites. Control mice were immunized once without prior T-cell transfer. Twelve days after the last immunization, animals were challenged by i.v. injection of 10,000 sporozoites of the corresponding genotype. After 42 h, livers were removed and parasite loads were quantified by real-time PCR. Bars and whiskers show means ± standard deviations. *, P < 0.05; **, P < 0.01 (Mann-Whitney test).

Mentions: To address the functional relevance of antigen-specific CD8+ and CD4+ T cells to protection in this immunization and infection model, we tested the contribution of OVA-specific T cells to inhibition of Plasmodium liver-stage development in vivo. We transferred 2 × 105 nonactivated OT-I (CD8) and OT-II (CD4) T cells each into mice, and 24 h later, immunized the recipient animals with 10,000 irradiated normal or transgenic OVA sporozoites (Fig. 5). Ten days later, the mice were challenged with the respective sporozoite lines used for immunization. Control mice did not receive OVA-specific T cells before immunization.


Antigen export during liver infection of the malaria parasite augments protective immunity.

Montagna GN, Beigier-Bompadre M, Becker M, Kroczek RA, Kaufmann SH, Matuschewski K - MBio (2014)

Immunization with expOVA sporozoites enhances protection against reinfection. (A) Quantification of parasite liver loads in immunized mice that received OT-1 or OT-2 cells. C57BL/6 mice received 2 × 105 OT-I (CD8) T cells (OT-1) or OT-II (CD4) T cells (OT-2). Next, mice were immunized once with 10,000 irradiated WT (black), expOVA (red), or OVA (green) sporozoites. Control mice were immunized once without prior T-cell transfer. Twelve days after the last immunization, animals were challenged by i.v. injection of 10,000 sporozoites of the corresponding genotype. After 42 h, livers were removed and parasite loads were quantified by real-time PCR. Bars and whiskers show means ± standard deviations. *, P < 0.05; **, P < 0.01 (Mann-Whitney test).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4128355&req=5

fig5: Immunization with expOVA sporozoites enhances protection against reinfection. (A) Quantification of parasite liver loads in immunized mice that received OT-1 or OT-2 cells. C57BL/6 mice received 2 × 105 OT-I (CD8) T cells (OT-1) or OT-II (CD4) T cells (OT-2). Next, mice were immunized once with 10,000 irradiated WT (black), expOVA (red), or OVA (green) sporozoites. Control mice were immunized once without prior T-cell transfer. Twelve days after the last immunization, animals were challenged by i.v. injection of 10,000 sporozoites of the corresponding genotype. After 42 h, livers were removed and parasite loads were quantified by real-time PCR. Bars and whiskers show means ± standard deviations. *, P < 0.05; **, P < 0.01 (Mann-Whitney test).
Mentions: To address the functional relevance of antigen-specific CD8+ and CD4+ T cells to protection in this immunization and infection model, we tested the contribution of OVA-specific T cells to inhibition of Plasmodium liver-stage development in vivo. We transferred 2 × 105 nonactivated OT-I (CD8) and OT-II (CD4) T cells each into mice, and 24 h later, immunized the recipient animals with 10,000 irradiated normal or transgenic OVA sporozoites (Fig. 5). Ten days later, the mice were challenged with the respective sporozoite lines used for immunization. Control mice did not receive OVA-specific T cells before immunization.

Bottom Line: A fundamental question is whether recognition by effector CD8(+) T cells is restricted to sporozoite surface antigens or extends to parasite proteins that are synthesized during the extensive parasite expansion phase in the liver.Using a surrogate model antigen, we found that a cytoplasmic antigen is able to induce robust protective CD8(+) T-cell responses, but protein export further enhances immunogenicity and protection.Our results show that a cytoplasmic localization does not exclude a protein's candidacy for malaria subunit vaccines and that protein secretion can enhance protective immunity.

View Article: PubMed Central - PubMed

Affiliation: Parasitology Unit, Max Planck Institute for Infection Biology, Berlin, Germany montagnageo@gmail.com.

Show MeSH
Related in: MedlinePlus