Illustration of mpox

Laboratory of Transmission Immunology

Transmission of viruses is only possible during a specific time frame after infection: we can call this the “window of transmission”. A major gap in mitigating (e.g., airborne) transmission and closing this window quickly is the lack of understanding of critical immune determinants of efficient transmission. To be able to close the window of transmission through the design of better mitigation strategies, we develop a mechanistic understanding of the spatial and longitudinal interplay between virus tropism, innate and adaptive immune responses, changes in host physiology, and exhalation or shedding of infectious virus in droplets or fluids.

Dr Julia Port

Head

Dr Julia Port
Research Group Leader

Graphical representation of the research objectives

Two of the largest pandemics in the last century, with massive global health and economic impacts, were caused by zoonotic respiratory RNA viruses able to transmit through the air: the 1918 influenza A virus and the betacoronavirus SARS-CoV-2. We know that SARS-CoV-2 is highly efficient at airborne transmission. In comparison, the initial SARS-CoV-1 outbreak was stopped from reaching the same pandemic state because this virus, like Middle Eastern Respiratory Syndrome (MERS)-CoV, presented with less airborne transmission potential. While transmission through respiratory droplets has been posited for all betacoronaviruses, what mechanistically differentiates the transmission potential of these betacoronaviruses is not well understood. Even less is known of more distantly related seasonal human coronaviruses (e.g., HCoV-OC43), which account for up to 35% of adult respiratory infections during peak periods. For respiratory viruses, we do not fully grasp how infection and mucosal immune responses against the infection affect the size, quantity, and physicochemical make-up of droplets in which the virus is exhaled. Therefore, transmission in humans is multifactorial and needs a multidisciplinary rather than a rudimentary experimental approach. To this end, the lab bridges immunology with aerobiology and environmental virology.

The work of the group builds around these three central questions:

  1. How does immunopathogenesis modulate the window of successful transmission?
  2. How does pre-existing immunity influence onward transmission?
  3. How does infection modulate the exhaled or secreted droplets and fluids that carry infectious viruses?
Illustration of the transmission of respiratory pathogens

To address these questions, we elucidate the conserved mechanisms of transmission and those that distinguish a highly transmissible virus from a member of the same family (e.g., betacoronaviruses), which caused a self-limited outbreak, using in vitro and ex vivo airway and mucosal models and in vivo transmission studies. We decipher how the site of initial virus replication and subsequent differences in immunopathogenesis and mucus composition impact virus release into the air or bodily secretions.

We study waning cellular and humoral immune responses to viral infections and correlate these immune parameters to the quantity and quality of transmission blockage upon renewed challenge with the same and with related viruses.

Lastly, we investigate whether the quantity and quality of (respiratory) droplets and secretions affect transmissibility. For respiratory viruses, we define the distribution of infectious viruses across different droplet sizes and analyze the exhaled droplet make-up and physicochemical properties, which inform virus stability studies.

This approach will allow us to understand the mechanistic underpinnings of viral transmission and will identify immune signatures linked to an increased risk of onward transmission.