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The Challenges of Developing and Applying an HCV Vaccine

"Dahari Lab is committed to the WHO goal of global HCV elimination"

Models indicate that the goal of hepatitis C virus (HCV) elimination by 2030 put forth by the World Health Organization is possible in theory. The reality is a bit more complicated. While it is possible through treatment alone without developing a vaccine, reinfections in specialty groups can cancel out any progress made in reducing HCV elsewhere in the population. Models have shown that a variety of treatment strategies yield just as many outcomes with a number of tradeoffs. This is confirmed in the data from models built to explore the impact of various treatment approaches to HCV. Developing a vaccine for HCV has many benefits that should not be seen as luxuries or an afterthought. An effective vaccine would reduce treatment cost and duration; prevent new cases; and allow research funding and focus to shift, all on a global scale.

 

Our research at Dahari Lab, along with our partners/collaborators, has contributed to each of these areas. Our 2019 research on treatment and intervention in the special population of people who inject drugs (PWID) in Chicago used mathematical modeling to show the impact of four different treatment interventions. The results showed a combination of direct-acting antivirals (DAAs) plus a vaccine was, by far, the most efficient and cost-effective treatment option. Both incidence and prevalence were significantly impacted and the WHO goal of 90% incidence reduction was achieved in the most efficient way (Vaccine). Even if the vaccine developed was not 100% effective in achieving sterilized immunity (but dramatically reduced the amount of viral load in the blood) it would still greatly reduce the ability for HCV to be transmitted to others. Our study focused on PWID population scenario as these specialty groups while a small percentage represent a higher level of infection, reinfection and transmission (Sci Transl Med). A vaccine which reduces viral load is also important for other specialty groups like healthcare workers. They are exposed to risk frequently and in some cases may not even be aware of the risk in a low-risk, routine environment like a computerized tomography (CT) scan. The risk factors are elevated because people (especially with chronic) HCV are typically asymptomatic. Another major challenge is the vast majority of HCV cases worldwide have not been diagnosed and people are unaware they are infected, much less infecting others. This puts groups typically at low risk in the broader population at a higher risk for infection. This can be especially problematic for healthcare workers or other individuals exposed to even the smallest amount of infected blood (PLoS One).

 

A vaccine that was not a fully sterilizing vaccine but simply reduced the viral load, would greatly reduce the chances of “unknown” infections in low-risk environments as well as known high-risk populations such as PWID or victims of the opioid crisis. This is a critical contribution to the strategy of HCV elimination. These special populations can also present challenges in designing HCV vaccine trials. Through the use of modelling we are currently exploring how to optimize vaccine trial design for PWID and the challenges associated with this group.

The quest for controlled human infection (CHI) models to accelerated HCV vaccine development

The development of a controlled human infection (CHI) model for the hepatitis C virus (HCV), is considered essential for advancing vaccine research. The design of a CHI model requires careful consideration of the key elements including viral inoculum size, viral clearance rates, and timing of blood sampling intervals for immunological evaluations. Those elements must be fully understood for further development of a final study protocol.

 

Analyzing early viral-host kinetics immediately after time of infection and developing theoretical modeling tools are important aspects for addressing the fore-mentioned key elements to successfully design HCV vaccine trials in the CHI model.

 

A two-step clinical trial in CHI has been recently proposed, with the first step to define viral inoculum and establish viral-host kinetic picture in the absence of any vaccination. Existing chimeric mice with humanized livers that lack of adaptive immune response has the potential to serve as an appropriate preclinical tool to studying early HCV-host interactions.

 

Dahari Lab is focused in developing theoretical models to evaluate and provide insights into the interplay between HCV and host immune response for the design protocols of CHI model studies. This approach aims to replicate the early stages of acute HCV infection, drawing from historical data and mathematical modeling on acute HCV infections in chimpanzees, and is a promising step towards the much-needed HCV vaccine.

It is still under discussions not actually happening thus far

 

Click here for the full extent of our lab's research!

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