Study with Brazilian researcher brings future vaccine against malaria vivax to light
Finding of a new blood cell entry changes what is known about P. vivax14/02/2018
Marcelo Urbano Ferreira, one of Brazils leading malaria experts, is one of the researchers involved in the study recently published in Science entitled Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax. The paper shows that antibodies against PvRBP2b partially block the invasion in reticulocytes by P. vivax, suggesting an interesting target for vaccine development. Parasites from Brazilian and Thai patients were used for antibody tests. Among them, an inhibition of up to 64% reticulocyte invasion was achieved.
According to Dr. Ferreira, until now, it was known that Plasmodium vivax preferably invades reticulocytes, especially those very young that still express transferrin receptor -1 (TfR1), also known as CD71, in its surface. The novelty brought by this workis the identification of TfR1 as a receptor for P. vivax merozoite entry in reticolocytes, explaining its preference for this celular type, he details. Besides this, the work identifies the P. vivax molecule that interacts with TfR1 during the invasion process; it is one of the P. vivax reticulocyte binding proteins, known as PvRBP2.
To the researcher, the wide international cooperation allowed this novel finding to come to light. The main part of the work was held in Australia by the group lead by Dr. Wai-Hong Tham, who has final merit for the finding. The other researchers joined the specific tasks in the work outlined by her. Along with Dr. Manoj Duraisinghs group, from Harvard School of Public Health (also a co-author of the paper), we have enhanced short-term in vitro P. vivax culture strategies for use in reticulocyte re-invasion assays. These assays were critical to evidence the anti-PvRBP2b antibody inhibitory effect during the invasion process, he adds.
Dr. Duraisinghs group also standardized in vitro P. vivax invasion assays in a erythroleukemia cell strain (JK-1). The interesting thing is that these cells can be genetically modified, for example, by using CRISPR/Cas9 (a genome edition system widely used nowadays). This way, Dr. Duraisingh produced JK-1 cell derivative reticulocytes that do not express TfR1 and showed they are refractory to P. vivax invasion (that depends on this receptor) but not by P. falciparum (that does not need this repector).
According to Dr. Ferreira, now, several groups are trying to describe naturally acquired responses of antibodies against PvRBP2b to know whether they are protectors against P. vivax infection. In other words, if the presence of such antibodies can be seen as an acquired immune marker against malaria vivax. This is one of our goals while colaborating with Dr. Tham, he stresses.
The expert believes in a long term it will be natural that PvRBP2b to be seen as an important candidate for the development of vaccines against malaria vivax. The optimism level regarding the development and use of vaccines against malaria is very variable among reserachers in the field, but this is still a possible outcome of this work, he says.
Finally, Dr. Ferreira stresses Brazils strategic relevance as an endemic country with large malaria research capacity.…