Publication Q&A: Antibody interference by a non-neutralizing antibody abrogates humoral protection against Plasmodium yoelii liver stage

August 2021 – Drs. Alexis Kaushansky, Noah Sather and Kamalakannan Vijayan from the Center for Global Infectious Disease Research at Seattle Children’s share insights from a recent publication in Cell Reports.

In this publication, the team shows that previous exposure to malaria can alter vaccine efficacy in animal models.

Seattle Children’s contributing authors include Kamalakannan Vijayan, Ganesh Ram R. Visweswaran, Olesya Trakhimets, Alexander Watson, Nicholas Dambrauskas, Andrew Raappana, Elizabeth K.K. Glennon, D. Noah Sather and Alexis Kaushansky

Antibody interference by a non-neutralizing antibody abrogates humoral protection against Plasmodium yoelii liver stage

Read this publication in Cell Reports.

What are the significant findings in this paper?

Most work on the development of malaria vaccines happens in laboratory or clinical trials where people or experimental conditions are “malaria naïve” – meaning that they mimic the first time that a person is infected with malaria. Yet, this is not how things happen in the real world – in malaria-endemic areas, people are often infected by malaria many times a year, and thus harbor what we call “pre-existing immunity” to malaria infection. Unfortunately, vaccines don’t work as well in this setting. In this publication, we explore how this pre-existing immunity might impact vaccination to malaria. We show that pre-existing immunity can decrease how well vaccination works in animal model of malaria.

What does this research tell us that we did not know before?

One of the big questions in malaria vaccine research is why vaccines don’t work as well in areas with a lot of malaria exposure. We have shown that an antibody that can develop against the malaria parasite, but does not stop infection can actually decrease the efficacy of vaccination.

What are the broad implications of this research?

We hope our findings will help design malaria vaccines be more effective in people who exposed many times to malaria throughout their lives.

What are the next steps and long-term goals for this research?

Our publication provides proof-of-concept that previous exposure and immune response can alter vaccine success. First, we need to explore if this is the case in humans, not simply animal models. Second, we need to better understand how this works on a molecular level, so we can intervene. Finally, we call for vaccine developers to take this into account when developing the next round of malaria vaccine candidates.

Any other specific information should we know about this paper?

This work was a collaboration between the Kaushansky Lab (that studies host-pathogen interactions) and the Sather Lab (that studies vaccine development and B-cell biology), and could not have been accomplished without the expertise from both laboratories.