Field research on malaria vaccine offers unexpected surprise

Field research on the effectiveness of a malaria vaccine, came up with unexpected  results for an international group of researchers including Benjamin Mordmüller of Radboudumc. The vaccine evokes a broader response against malaria proteins than there are in the vaccine, they write in The Journal of Clinical Investigation.

Mosquirix (RTS,S/AS01E) is the first vaccine recommended by the WHO for use in African children to prevent malaria. This vaccine targets Plasmodium falciparum, the deadliest malaria species in humans. The vaccine contains a protein that is on the surface of the parasite at its sporozoite stage. The sporozoite is the stage of the malaria parasite that enters the human body through a mosquito bite, where it travels to the liver. The vaccine is aimed at rendering the malaria parasite harmless exactly at that stage through antibodies that are produced in response to the vaccine. 

Vaccine induced immune response

Benjamin Mordmüller of the Radboudumc Department of Medical Microbiology has been working with the MAL076 Vaccine Immunology Consortium and Antigen Discovery Inc. to study how the vaccine works in practice. "We looked at the development of immune responses against 1,000 malaria antigens in more than 2,000 children participating in a phase 3 clinical trial," says Mordmüller. "Primarily, to see how the immune response to the parasite is altered by the vaccine."

Broader protection

Remarkably, they saw that vaccination led to strong reactions against several other malaria proteins beside the vaccine. Mordmüller: "We also found strong reactions against malaria proteins that were not part of the vaccine. We wondered how this was possible. Did some vaccinees get more exposed to the parasite? But in practice we found no evidence of that." 

Off-target responses

The researchers now think that the broader protection may arise from a kind of cross-reaction. In this process, the body not only produces antibodies against the injected proteins, but a much broader immune response ensues. Mordmüller: "These off-target reactions occurred in about half of the participants and the recognized proteins do not show clear similarities to the vaccine. We are currently investigating if the same antibodies recognize different proteins or if a bystander reaction occurs. But from a vaccination and protection point of view, the most important news is that the off-target reactions that occur in a portion of the children provide better protection against malaria. That's an unexpected windfall."
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Paper in JCI Insight: Strong off-target antibody reactivity to malarial antigens induced by RTS,S/AS01E vaccination is associated with protection - Dídac Macià, Joseph J. Campo, Gemma Moncunill, Chenjerai Jairoce, Augusto J. Nhabomba, Maximilian Mpina, Hermann Sorgho, David Dosoo, Ousmane Traore, Kwadwo A. Kusi, Nana Aba Williams, Amit Oberai, Arlo Randall, Hector Sanz, Clarissa Valim, Kwaku P. Asante, Seth Owusu-Agyei, Halidou Tinto, Selidji T. Agnandji, Simon Kariuki, Ben Gyan, Claudia Daubenberger, Benjamin Mordmüller, Paula Petrone and Carlota Dobaño

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