A summary by Adrian Wildfire - CEO CHIMunomics
The great and the good ... and myself 😉 , gathered in Rockville to discuss influenza CHIM (CHIVIM) and how best to advance the model to provide prognostic results for drugs, vaccines and also transmission studies.
Modelling transmission with comparable secondary attack rates in influenza has proved remarkably difficult, despite successes in animal modelling, primarily in ferrets. To give a flavour to the proceedings re measurable viral shedding correlates and concomitant immune parameters, results from the SARS-CoV-2 challenge study by Imperial were presented in the opening session. Interesting data were shown regarding infection (true, negative and ‘blipping’ subjects), with viral load (peak and vAUC) and individual live virus shedding showing little correlation. This may bode ill for simple SAR studies in COVID, which may possibly also translate across to influenza. It is possible that measuring CD8 activation and early IFNy promotion will be required going forward if cohorts are to be better managed both for safety and susceptibility to disease.
A representative spectrum of disease is what CHIVIM needs to aim for but has largely eluded the modellers thus far.
The discussion on the ethics and regulation of CHIVIM brought up some familiar issues. The movement towards ‘risk’ being incorporated into calculations of remuneration is interesting. Despite the negative connotation, the public seems to view risk more favourably than academics do. Consultations generally support rewarding individuals engaging in 'risky' behaviors for the public good, such as firefighters, police, and mountain rescue teams. Does this affect the payments to be made to ‘endemic populations’ where immunity may be higher? Likely so. There's a need for balance, ensuring fair rewards based on local standards and avoiding inappropriate translation from HIC to LMIC countries.
Industry players gave good account of the (largely positive) use of CHIVIM in advancing commercial products. However, there is still some way to go regarding translation e.g. appropriate serological screening, better standardisation of assays and correlates. A lot of work is still needed to understand even the accepted basics of CHIVIM such as inoculating titre (what is the infective titre in the community?), prior T cell priming, route of inoculation (nose, mouth, mucous membranes), method of inoculation and correlates of protection and efficacy.
HAI is losing favour but what to replace it with is still of some debate. Even the choice of the challenge agents (origin, strain, ‘hot’ (wild type) or not) and the method of manufacturing them is still not agreed. E.g. reverse genetics-derived agents being considered GMOs, may be hold back in many countries, yet egg manufacture may encourage genomic changes and lower lung tropism. Even cell line manufacture is limited by the choice of approved cell line available. Good news on the latter is that NIH is making progress with new availabilities for MDCK and HEK293 cell lines. Watch this space!
With the VTEU / CIVIC and other CHIVIM centres coming online as new agents are provided, this presents an opportune moment for influenza modelers, as there are significant objectives on the horizon. These include developing mucosal vaccines to stop transmission, and enhancing the effectiveness and scope of coverage for seasonal vaccines against epidemic strains.
I look forward to the next meeting to see how far we have met the challenges discussed or to find out whether other priorities have intervened.
