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Immunization with L. sigmodontis microfilariae reduces peripheral microfilaraemia after challenge infection by inhibition of filarial embryogenesis.

Ziewer S, Hübner MP, Dubben B, Hoffmann WH, Bain O, Martin C, Hoerauf A, Specht S - PLoS Negl Trop Dis (2012)

Bottom Line: Protection was associated with the impairment of intrauterine filarial embryogenesis and with local and systemic microfilarial-specific host IgG, as well as IFN-γ secretion by host cells from the site of infection.Furthermore immunization significantly reduced adult worm burden.Our results present a tool to understand the immunological basis of vaccine induced protection in order to develop a microfilariae-based vaccine that reduces adult worm burden and prevents microfilaraemia, a powerful weapon to stop transmission of filariasis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.

ABSTRACT

Background: Lymphatic filariasis and onchocerciasis are two chronic diseases mediated by parasitic filarial worms causing long term disability and massive socioeconomic problems. Filariae are transmitted by blood-feeding mosquitoes that take up the first stage larvae from an infected host and deliver it after maturation into infective stage to a new host. After closure of vector control programs, disease control relies mainly on mass drug administration with drugs that are primarily effective against first stage larvae and require many years of annual/biannual administration. Therefore, there is an urgent need for alternative treatment ways, i.e. other effective drugs or vaccines.

Methodology/principal findings: Using the Litomosoides sigmodontis murine model of filariasis we demonstrate that immunization with microfilariae together with the adjuvant alum prevents mice from developing high microfilaraemia after challenge infection. Immunization achieved 70% to 100% protection in the peripheral blood and in the pleural space and furthermore strongly reduced the microfilarial load in mice that remained microfilaraemic. Protection was associated with the impairment of intrauterine filarial embryogenesis and with local and systemic microfilarial-specific host IgG, as well as IFN-γ secretion by host cells from the site of infection. Furthermore immunization significantly reduced adult worm burden.

Conclusions/significance: Our results present a tool to understand the immunological basis of vaccine induced protection in order to develop a microfilariae-based vaccine that reduces adult worm burden and prevents microfilaraemia, a powerful weapon to stop transmission of filariasis.

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Related in: MedlinePlus

Mice immunized with Mf in alum have reduced numbers of Mf.Mice were immunized three times s.c. with 100,000 Mf in alum. Control mice received alum alone. L. sigmodontis infection was performed one week after the last immunization. Microfilaraemia was monitored twice a week throughout patency. (A) Kinetics of Mf load of sham-treated (dashed line) and immunized (black line) mice in the peripheral blood. One representative of three independent experiments with ten mice per group is shown (2-way ANOVA, mean ± SEM), including both Mf− and Mf+ mice. For additional experiments see figure S3A, B. (B) Percentage of Mf+ mice of three independent experiments was analyzed using Student's t-test. Each mouse with peripheral Mf at any given time point was defined as Mf+. (C, D) Mf burden in the pleural space days 70 (C) and 90 (D) p.i.. Graphs show one representative of three (C) and two (D) independent experiments (at least seven mice each group, see also Figure S3C–E) and were analyzed with Welch-corrected t-test. Numbers below the symbols indicate the number of Mf+ mice (median, * P<0.05, ** P<0.005).
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pntd-0001558-g002: Mice immunized with Mf in alum have reduced numbers of Mf.Mice were immunized three times s.c. with 100,000 Mf in alum. Control mice received alum alone. L. sigmodontis infection was performed one week after the last immunization. Microfilaraemia was monitored twice a week throughout patency. (A) Kinetics of Mf load of sham-treated (dashed line) and immunized (black line) mice in the peripheral blood. One representative of three independent experiments with ten mice per group is shown (2-way ANOVA, mean ± SEM), including both Mf− and Mf+ mice. For additional experiments see figure S3A, B. (B) Percentage of Mf+ mice of three independent experiments was analyzed using Student's t-test. Each mouse with peripheral Mf at any given time point was defined as Mf+. (C, D) Mf burden in the pleural space days 70 (C) and 90 (D) p.i.. Graphs show one representative of three (C) and two (D) independent experiments (at least seven mice each group, see also Figure S3C–E) and were analyzed with Welch-corrected t-test. Numbers below the symbols indicate the number of Mf+ mice (median, * P<0.05, ** P<0.005).

Mentions: Finally, to investigate whether a standard adjuvant is able to establish protective immunity, mice were then immunized three times with 100,000 Mf together with the adjuvant alum. Due to the viscosity of alum this immunization was performed s.c.. Mice immunized with Mf in alum had significantly reduced numbers of circulating Mf after challenge infection compared to control animals throughout patency (P<0.05, Figure 2A). Furthermore, the frequency of mice that became microfilaraemic until the end of observation was significantly reduced in the immunized group (P<0.05, Figure 2B).


Immunization with L. sigmodontis microfilariae reduces peripheral microfilaraemia after challenge infection by inhibition of filarial embryogenesis.

Ziewer S, Hübner MP, Dubben B, Hoffmann WH, Bain O, Martin C, Hoerauf A, Specht S - PLoS Negl Trop Dis (2012)

Mice immunized with Mf in alum have reduced numbers of Mf.Mice were immunized three times s.c. with 100,000 Mf in alum. Control mice received alum alone. L. sigmodontis infection was performed one week after the last immunization. Microfilaraemia was monitored twice a week throughout patency. (A) Kinetics of Mf load of sham-treated (dashed line) and immunized (black line) mice in the peripheral blood. One representative of three independent experiments with ten mice per group is shown (2-way ANOVA, mean ± SEM), including both Mf− and Mf+ mice. For additional experiments see figure S3A, B. (B) Percentage of Mf+ mice of three independent experiments was analyzed using Student's t-test. Each mouse with peripheral Mf at any given time point was defined as Mf+. (C, D) Mf burden in the pleural space days 70 (C) and 90 (D) p.i.. Graphs show one representative of three (C) and two (D) independent experiments (at least seven mice each group, see also Figure S3C–E) and were analyzed with Welch-corrected t-test. Numbers below the symbols indicate the number of Mf+ mice (median, * P<0.05, ** P<0.005).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3295809&req=5

pntd-0001558-g002: Mice immunized with Mf in alum have reduced numbers of Mf.Mice were immunized three times s.c. with 100,000 Mf in alum. Control mice received alum alone. L. sigmodontis infection was performed one week after the last immunization. Microfilaraemia was monitored twice a week throughout patency. (A) Kinetics of Mf load of sham-treated (dashed line) and immunized (black line) mice in the peripheral blood. One representative of three independent experiments with ten mice per group is shown (2-way ANOVA, mean ± SEM), including both Mf− and Mf+ mice. For additional experiments see figure S3A, B. (B) Percentage of Mf+ mice of three independent experiments was analyzed using Student's t-test. Each mouse with peripheral Mf at any given time point was defined as Mf+. (C, D) Mf burden in the pleural space days 70 (C) and 90 (D) p.i.. Graphs show one representative of three (C) and two (D) independent experiments (at least seven mice each group, see also Figure S3C–E) and were analyzed with Welch-corrected t-test. Numbers below the symbols indicate the number of Mf+ mice (median, * P<0.05, ** P<0.005).
Mentions: Finally, to investigate whether a standard adjuvant is able to establish protective immunity, mice were then immunized three times with 100,000 Mf together with the adjuvant alum. Due to the viscosity of alum this immunization was performed s.c.. Mice immunized with Mf in alum had significantly reduced numbers of circulating Mf after challenge infection compared to control animals throughout patency (P<0.05, Figure 2A). Furthermore, the frequency of mice that became microfilaraemic until the end of observation was significantly reduced in the immunized group (P<0.05, Figure 2B).

Bottom Line: Protection was associated with the impairment of intrauterine filarial embryogenesis and with local and systemic microfilarial-specific host IgG, as well as IFN-γ secretion by host cells from the site of infection.Furthermore immunization significantly reduced adult worm burden.Our results present a tool to understand the immunological basis of vaccine induced protection in order to develop a microfilariae-based vaccine that reduces adult worm burden and prevents microfilaraemia, a powerful weapon to stop transmission of filariasis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.

ABSTRACT

Background: Lymphatic filariasis and onchocerciasis are two chronic diseases mediated by parasitic filarial worms causing long term disability and massive socioeconomic problems. Filariae are transmitted by blood-feeding mosquitoes that take up the first stage larvae from an infected host and deliver it after maturation into infective stage to a new host. After closure of vector control programs, disease control relies mainly on mass drug administration with drugs that are primarily effective against first stage larvae and require many years of annual/biannual administration. Therefore, there is an urgent need for alternative treatment ways, i.e. other effective drugs or vaccines.

Methodology/principal findings: Using the Litomosoides sigmodontis murine model of filariasis we demonstrate that immunization with microfilariae together with the adjuvant alum prevents mice from developing high microfilaraemia after challenge infection. Immunization achieved 70% to 100% protection in the peripheral blood and in the pleural space and furthermore strongly reduced the microfilarial load in mice that remained microfilaraemic. Protection was associated with the impairment of intrauterine filarial embryogenesis and with local and systemic microfilarial-specific host IgG, as well as IFN-γ secretion by host cells from the site of infection. Furthermore immunization significantly reduced adult worm burden.

Conclusions/significance: Our results present a tool to understand the immunological basis of vaccine induced protection in order to develop a microfilariae-based vaccine that reduces adult worm burden and prevents microfilaraemia, a powerful weapon to stop transmission of filariasis.

Show MeSH
Related in: MedlinePlus