Abstract
BackgroundHuman populations that are naturally subjected to Plasmodium infection do not acquire complete protection against the liver stage of this parasite despite prolonged and frequent exposure. However, sterile immunity against Plasmodium liver stage can be achieved after repeated exposure to radiation attenuated sporozoites. The reasons for this different response remain largely unknown, but a suppressive effect of blood stage Plasmodium infection has been proposed as a cause for the lack of liver stage protection.MethodsUsing Plasmodium yoelii 17XNL, the response generated in mice subjected to daily infective bites from normal or irradiated mosquitoes was compared. The effect of daily-infected mosquito bites on mice that were previously immunized against P. yoelii liver stage was also studied.ResultsIt was observed that while the bites of normal infected mosquitoes do not generate strong antibody responses and protection, the bites of irradiated mosquitoes result in high levels of anti-sporozoite antibodies and protection against liver stage Plasmodium infection. Exposure to daily infected mosquito bites did not eliminate the protection acquired previously with a experimental liver stage vaccine.ConclusionsLiver stage immunity generated by irradiated versus normal P. yoelii infected mosquitoes is essentially different, probably because of the blood stage infection that follows normal mosquito bites, but not irradiated. While infective mosquito bites do not induce a protective liver stage response, they also do not interfere with previously acquired liver stage protective responses, even if they induce a complete blood stage infection. Considering that the recently generated anti-malaria vaccines induce only partial protection against infection, it is encouraging that, at least in mouse models, immunity is not negatively affected by subsequent exposure and infection with the parasite.
Highlights
Human populations that are naturally subjected to Plasmodium infection do not acquire complete protection against the liver stage of this parasite despite prolonged and frequent exposure
This result again confirms the concordance of observations in mice and in humans regarding liver stage immunity and focuses the questions about generation of liver stage protection on the differences between infection generated by irradiated versus normal sporozoites
The results presented show that the liver stage immunity generated in response to irradiated versus normal P. yoelii infected mosquitoes is essentially different: while irradiated mosquitoes induce a protective immune response with high levels of anti-sporozoite antibodies, normal infected mosquitoes do not generate protection and only low levels of specific antibodies
Summary
Human populations that are naturally subjected to Plasmodium infection do not acquire complete protection against the liver stage of this parasite despite prolonged and frequent exposure. The subunit vaccines are the most advanced in research pipelines and field clinical trials [1], an effective and focused effort prevails in order to develop an attenuated sporozoite-based vaccine [2,3], once the protective [10]. In this work, it was assessed whether the daily bites of non-irradiated infected mosquitoes would induce a protective liver stage immune response, similar to that induced by irradiated infected mosquito bites. This result again confirms the concordance of observations in mice and in humans regarding liver stage immunity and focuses the questions about generation of liver stage protection on the differences between infection generated by irradiated versus normal sporozoites
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