Research roadmap for coronavirus vaccine development

Download 202402 Draft Coronavirus Vaccine research roadmap Final

Host responses to natural infection

visit roadmap

Dependencies

17 Host-pathogen interactions
17A Entry
17B Replication
17C Persistence/ clearance

Next steps

Host responses to natural infection

Research Question

What are we trying to achieve? Gain a better understanding of host response to natural infection to inform vaccine development strategies and understand disease pathology in animal models
Problem? Generally, the same/similar model systems are used to understand pathology, transmission and response to infection to novel pathogens, based on established models for similar viruses. However, this may not be the most physiologically relevant model. There is a lack of knowledge and research on animal immunology for e.g., birds, pets, wildlife – some work has been done to advance understanding of porcine and bovine immunology, but not as much as in mice and humans.

Research Gaps and Challenges

Accuracy: Not all animal models mimic natural infection well, and may be exaggerated or inaccurate because the virus being used may not usually be able to infect that host. Also, inbred vs outbred animals may yield varied immune responses
Immunity: There is a need to test long-term immunity to both natural infection and after vaccination. Measuring more than just nAb responses – T-cell response, muscosal, non-neutralizing Ab responses (ADCC, complement etc). Can we identify immune response markers that are freely/widely available (that provide broad protection)?
Selecting the correct animal model: Deciding which animal model to use that will support virus infection and replication to study disease is important as this may not be the same for all coronaviruses, e.g., change to hamster model for SARS-CoV-2 due to lack of productive infection in ferret model
Other factors: Understanding the role of pre-exposure to a pathogen, co-infections of other pathogens, the role of innate immunity and age to host response. All these factors will impact a host’s response to natural infection. Quality control is not available from a lot of commercial companies
Lack of resources to measure immune response: There are many resources available for mouse models to look at, for e.g., cytokine responses, setting up large flow cytometry panels to look at immune cell profiles; however, these resources are less available or established for other animal models, reducing the amount of information we are able to obtain. Lack of, for e.g. pig interferons so that human interferons have to be used

Solution Routes

Resources: Developing tools and resources to broaden the immune response that can be characterised in less –well-established animal models
Challenge studies: Experimental challenge studies on long-term immunity in both natural infection and after vaccination – best addressed initially in natural host systems. More bioinformatics needed: Predicting similarity at sequence/protein level using whole animal genome study data to resources that could be broad-acting

Dependencies

Establishing animal models in natural host systems for where this is not yet done
Requirement of developing more specific reagents. Is there a way for industry (animal vaccine producers) and academia to work together to support the development of non-human immunological toolboxes? Why have these not succeeded at a global level previously? Could this be something that IVVN could lead on?
Understand innate and adaptive immune pathways in animal models and accurately document what disease and transmission looks like in these animals
Better One-Health collaboration: Needs to be more exchange of knowledge/experience from researchers working on vet vs human vaccines – vet field were immunising animals for decades against coronaviruses, but this prior knowledge is largely ignored when developing human vaccines

State Of the Art

SARS-CoV-2: Ferret model did not show productive infection when infected with SARS-CoV-2 (modelled off what was done for SARS-CoV1), so there was a transition to use the hamster model instead. Models established for PDV/TGEV to study infection and to test vaccine efficacy in pigs
Previous toolboxes established in Europe that have not been successful – what can we learn from these and what approaches do work? More success seen from individual groups