Reversing vaccine hypo-responsiveness

Introduction

Prevention of infectious diseases through vaccination is one of the greatest achievements of medicine. Yet, there is growing realization that vaccine immunogenicity and efficacy varies greatly across populations in high- versus low/middle-income countries (LMIC) and in urban- versus rural areas within one country.

Vaccine Efficacy Discrepancies

For example, whereas vaccination of volunteers in Europe with attenuated malaria vaccine can result in 100% protection, the efficacy drops to only 29% when tested in Africa, where it is needed most. Other vaccines, such as rotavirus, BCG, yellow fever, and Ebola show similar trends in either immunogenicity or efficacy.

Research Ambition

It is my ambition to take on the challenge of understanding the mechanisms underlying vaccine hypo-responsiveness across populations and find ways to REVERSE it.

Hypothesis

I hypothesize that the variation in the immunological network, shaped by exposure to microorganisms and parasites, as well as by the cellular metabolic state of populations residing in distinct environmental conditions, underlies vaccine hypo-responsiveness. This can be REVERSED by immunological and metabolic interventions.

Methodology

To address this, I will:

1. Compare unique cohorts from LMIC and Europe.
2. Use single-cell technologies to understand the immunological and metabolic networks that govern innate and adaptive immune responses.
3. Study not only blood but also secondary lymphoid organs to gain critical information on key cell-cell interactions within germinal centers.
4. Investigate how these interactions are influenced by cells beyond B and T cells, discovering key pathways underlying hypo-responsiveness.

Clinical Application

I will take advantage of the increasing availability of clinically approved modulatory compounds to target these pathways and improve vaccine responses in our in vitro models.

Future Directions

I will also perform a proof of concept clinical trial to establish a pipeline for translating the fundamental insights gained to human testing, paving the way to new horizons for vaccines to show their full potential worldwide.