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Mosquito Akirin as a potential antigen for malaria control.

da Costa M, Pinheiro-Silva R, Antunes S, Moreno-Cid JA, Custódio A, Villar M, Silveira H, de la Fuente J, Domingos A - Malar. J. (2014)

Bottom Line: Recent evidences using Subolesin (SUB) and Akirin (AKR) vaccines showed a reduction in the survival and/or fertility of blood-sucking ectoparasite vectors and the infection with vector-borne pathogens.If effective, AKR-based vaccines could be used to immunize wildlife reservoir hosts and/or humans to reduce the risk of pathogen transmission.However, these vaccines need to be evaluated under field conditions to characterize their effect on vector populations and pathogen infection and transmission.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Higiene e Medicina Tropical, Rua da Junqueira 100, 1349-008 Lisbon, Portugal. adomingos@ihmt.unl.pt.

ABSTRACT

Background: The control of vector-borne diseases is important to improve human and animal health worldwide. Malaria is one of the world's deadliest diseases and is caused by protozoan parasites of the genus Plasmodium, which are transmitted by Anopheles spp. mosquitoes. Recent evidences using Subolesin (SUB) and Akirin (AKR) vaccines showed a reduction in the survival and/or fertility of blood-sucking ectoparasite vectors and the infection with vector-borne pathogens. These experiments suggested the possibility of using AKR for malaria control.

Methods: The role of AKR on Plasmodium berghei infection and on the fitness and reproduction of the main malaria vector, Anopheles gambiae was characterized by evaluating the effect of akr gene knockdown or vaccination with recombinant mosquito AKR on parasite infection levels, fertility and mortality of female mosquitoes.

Results: Gene knockdown by RNA interference in mosquitoes suggested a role for akr in mosquito survival and fertility. Vaccination with recombinant Aedes albopictus AKR reduced parasite infection in mosquitoes fed on immunized mice when compared to controls.

Conclusions: These results showed that recombinant AKR could be used to develop vaccines for malaria control. If effective, AKR-based vaccines could be used to immunize wildlife reservoir hosts and/or humans to reduce the risk of pathogen transmission. However, these vaccines need to be evaluated under field conditions to characterize their effect on vector populations and pathogen infection and transmission.

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Effect of immunization with AKR on mosquito biology and infection withP. berghei. Mice were immunized with recombinant AKR or adjuvant/saline and then infected with P. berghei or left uninfected as controls. (A) Surviving mosquitoes. (B) Number of oocyst per midgut with representative fluorescence images of parasite oocyst in mosquito midguts. (C) Representative results for infection intensity. Similar results were obtained in all replicates (N = 5). (D) Representative results for infection rate. Similar results were obtained in all replicates (N = 5). (E) Number of eggs per ovary. (F) Oviposition (representative results for the number of laid eggs/mosquito; similar results were obtained in all replicates; N = 5). The number of parasite oocyst/midgut, eggs/ovary and the number of surviving mosquitoes (Ave ± SD) were compared between mosquitoes fed on immunized and control infected mice by a two-sample comparison using the non-parametric Mann–Whitney test (*P < 0.0001).
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Fig3: Effect of immunization with AKR on mosquito biology and infection withP. berghei. Mice were immunized with recombinant AKR or adjuvant/saline and then infected with P. berghei or left uninfected as controls. (A) Surviving mosquitoes. (B) Number of oocyst per midgut with representative fluorescence images of parasite oocyst in mosquito midguts. (C) Representative results for infection intensity. Similar results were obtained in all replicates (N = 5). (D) Representative results for infection rate. Similar results were obtained in all replicates (N = 5). (E) Number of eggs per ovary. (F) Oviposition (representative results for the number of laid eggs/mosquito; similar results were obtained in all replicates; N = 5). The number of parasite oocyst/midgut, eggs/ovary and the number of surviving mosquitoes (Ave ± SD) were compared between mosquitoes fed on immunized and control infected mice by a two-sample comparison using the non-parametric Mann–Whitney test (*P < 0.0001).

Mentions: To evaluate the effect of antibodies against AKR on the malaria vector An. gambiae and the infection with P. berghei, mice were immunized with recombinant mosquito AKR or placebo and infected with P. berghei parasites or left uninfected as controls. Mouse antibody titers increased after the first immunization with recombinant AKR and remained significantly higher until the end of the experiment in both AKR-immunized infected and uninfected mice when compared to controls (Figure 2). Different to akr knockdown, survival was not affected in mosquitoes fed on immunized mice when compared to mosquitoes fed on control mice (Figure 3A). Also in contrast to RNAi results, parasite infection was lower (Figures 3B-D) and egg production was higher (Figures 2E and F) in mosquitoes fed on immunized infected mice when compared to mosquitoes fed on control infected mice. Particularly relevant was the effect on infection intensity, which was reduced in more than 60-fold in mosquitoes fed on immunized mice when compared to controls (Figure 2C). Egg production was significantly lower in mosquitoes fed on immunized uninfected mice when compared to mosquitoes fed on control infected mice (Figure 2E).Figure 2


Mosquito Akirin as a potential antigen for malaria control.

da Costa M, Pinheiro-Silva R, Antunes S, Moreno-Cid JA, Custódio A, Villar M, Silveira H, de la Fuente J, Domingos A - Malar. J. (2014)

Effect of immunization with AKR on mosquito biology and infection withP. berghei. Mice were immunized with recombinant AKR or adjuvant/saline and then infected with P. berghei or left uninfected as controls. (A) Surviving mosquitoes. (B) Number of oocyst per midgut with representative fluorescence images of parasite oocyst in mosquito midguts. (C) Representative results for infection intensity. Similar results were obtained in all replicates (N = 5). (D) Representative results for infection rate. Similar results were obtained in all replicates (N = 5). (E) Number of eggs per ovary. (F) Oviposition (representative results for the number of laid eggs/mosquito; similar results were obtained in all replicates; N = 5). The number of parasite oocyst/midgut, eggs/ovary and the number of surviving mosquitoes (Ave ± SD) were compared between mosquitoes fed on immunized and control infected mice by a two-sample comparison using the non-parametric Mann–Whitney test (*P < 0.0001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4265507&req=5

Fig3: Effect of immunization with AKR on mosquito biology and infection withP. berghei. Mice were immunized with recombinant AKR or adjuvant/saline and then infected with P. berghei or left uninfected as controls. (A) Surviving mosquitoes. (B) Number of oocyst per midgut with representative fluorescence images of parasite oocyst in mosquito midguts. (C) Representative results for infection intensity. Similar results were obtained in all replicates (N = 5). (D) Representative results for infection rate. Similar results were obtained in all replicates (N = 5). (E) Number of eggs per ovary. (F) Oviposition (representative results for the number of laid eggs/mosquito; similar results were obtained in all replicates; N = 5). The number of parasite oocyst/midgut, eggs/ovary and the number of surviving mosquitoes (Ave ± SD) were compared between mosquitoes fed on immunized and control infected mice by a two-sample comparison using the non-parametric Mann–Whitney test (*P < 0.0001).
Mentions: To evaluate the effect of antibodies against AKR on the malaria vector An. gambiae and the infection with P. berghei, mice were immunized with recombinant mosquito AKR or placebo and infected with P. berghei parasites or left uninfected as controls. Mouse antibody titers increased after the first immunization with recombinant AKR and remained significantly higher until the end of the experiment in both AKR-immunized infected and uninfected mice when compared to controls (Figure 2). Different to akr knockdown, survival was not affected in mosquitoes fed on immunized mice when compared to mosquitoes fed on control mice (Figure 3A). Also in contrast to RNAi results, parasite infection was lower (Figures 3B-D) and egg production was higher (Figures 2E and F) in mosquitoes fed on immunized infected mice when compared to mosquitoes fed on control infected mice. Particularly relevant was the effect on infection intensity, which was reduced in more than 60-fold in mosquitoes fed on immunized mice when compared to controls (Figure 2C). Egg production was significantly lower in mosquitoes fed on immunized uninfected mice when compared to mosquitoes fed on control infected mice (Figure 2E).Figure 2

Bottom Line: Recent evidences using Subolesin (SUB) and Akirin (AKR) vaccines showed a reduction in the survival and/or fertility of blood-sucking ectoparasite vectors and the infection with vector-borne pathogens.If effective, AKR-based vaccines could be used to immunize wildlife reservoir hosts and/or humans to reduce the risk of pathogen transmission.However, these vaccines need to be evaluated under field conditions to characterize their effect on vector populations and pathogen infection and transmission.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Higiene e Medicina Tropical, Rua da Junqueira 100, 1349-008 Lisbon, Portugal. adomingos@ihmt.unl.pt.

ABSTRACT

Background: The control of vector-borne diseases is important to improve human and animal health worldwide. Malaria is one of the world's deadliest diseases and is caused by protozoan parasites of the genus Plasmodium, which are transmitted by Anopheles spp. mosquitoes. Recent evidences using Subolesin (SUB) and Akirin (AKR) vaccines showed a reduction in the survival and/or fertility of blood-sucking ectoparasite vectors and the infection with vector-borne pathogens. These experiments suggested the possibility of using AKR for malaria control.

Methods: The role of AKR on Plasmodium berghei infection and on the fitness and reproduction of the main malaria vector, Anopheles gambiae was characterized by evaluating the effect of akr gene knockdown or vaccination with recombinant mosquito AKR on parasite infection levels, fertility and mortality of female mosquitoes.

Results: Gene knockdown by RNA interference in mosquitoes suggested a role for akr in mosquito survival and fertility. Vaccination with recombinant Aedes albopictus AKR reduced parasite infection in mosquitoes fed on immunized mice when compared to controls.

Conclusions: These results showed that recombinant AKR could be used to develop vaccines for malaria control. If effective, AKR-based vaccines could be used to immunize wildlife reservoir hosts and/or humans to reduce the risk of pathogen transmission. However, these vaccines need to be evaluated under field conditions to characterize their effect on vector populations and pathogen infection and transmission.

Show MeSH
Related in: MedlinePlus