This week Nature Medicine published results from small trial involving controlled human malaria infection (CHMI) and experimental malaria vaccine developed by Sanaria (Sanaria Inc., Rockville, Maryland, USA). This vaccine based on attenuated Plasmodium falciparum sporozoite (abbreviated as PfSPZ vaccine) showed 55% efficacy at 1 year post-immunization.
Currently, only malaria vaccine available on market, RTS,S, has efficacy of ~ 22%. In this new study, scientists tested different dosages and routes of immunization for new PfSPZ vaccine as follows:
The results of the controlled human malaria infection are shown below. Here, healthy malaria-naive volunteers were first vaccinated and then received malaria infection from actual mosquitoes bites that carry malaria clone 3D7. The best outcomes were achieved with groups 4 and 5 (i.v. administration, 4 doses of 2.7 × 105 PfSPZ).
Next step was to understand immunological correlates of protection. However, this task was quite challenging, as it turned out. All vaccination protocols, with the exception of i.m. immunization, induced anti-malaria Ab or T cell responses. However, when vaccine trial participants were divided based on blood parasitemia following malaria challenge, it was observed that participants without parasitemia developed higher levels of anti-malaria serum Abs.
At the cellular level, however, the only marker that correlated with vaccine efficacy was frequency of unstimulated Vγ9+Vδ2+ γδ T cells which comprises ~75% of γδ T cells in blood. Actually, the frequency of Vγ9+Vδ2+ γδ T cells in pre-vaccinated individuals was the only marker that correlated with vaccine efficacy in challenge model.
In summary, this study showed that there is still room to improve malaria vaccine. Vaccine efficacy of 55% in 1-year followup is a significant progress when considering that In 2015 there were an estimated 214 million clinical cases of malaria in the world. Another outcome of this study is that fact that it is quite hard to find or define immune correlates of protection and this is especially true for parasitic infection such as malaria or dengue.
David Usharauli
Next step was to understand immunological correlates of protection. However, this task was quite challenging, as it turned out. All vaccination protocols, with the exception of i.m. immunization, induced anti-malaria Ab or T cell responses. However, when vaccine trial participants were divided based on blood parasitemia following malaria challenge, it was observed that participants without parasitemia developed higher levels of anti-malaria serum Abs.
At the cellular level, however, the only marker that correlated with vaccine efficacy was frequency of unstimulated Vγ9+Vδ2+ γδ T cells which comprises ~75% of γδ T cells in blood. Actually, the frequency of Vγ9+Vδ2+ γδ T cells in pre-vaccinated individuals was the only marker that correlated with vaccine efficacy in challenge model.
In summary, this study showed that there is still room to improve malaria vaccine. Vaccine efficacy of 55% in 1-year followup is a significant progress when considering that In 2015 there were an estimated 214 million clinical cases of malaria in the world. Another outcome of this study is that fact that it is quite hard to find or define immune correlates of protection and this is especially true for parasitic infection such as malaria or dengue.
David Usharauli
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