Human Challenge Study Design in Action - a Dengue Fever vaccine trial

A human challenge study, also known as a controlled human infection model (CHIM), is a type of clinical research study in which healthy volunteers are intentionally exposed to a specific pathogen (such as a virus, bacterium, or parasite) under controlled conditions. The primary goal of these studies is to better understand the pathogen's behavior, the human immune response to it, and to test the effectiveness of potential treatments, vaccines, or preventive measures. Human challenge studies can provide valuable insights into disease progression, immunity, and treatment efficacy in a controlled and ethical manner.

These studies are typically conducted under strict ethical and safety guidelines to minimize the risk to participants. Participants are closely monitored, and their informed consent is obtained. Human challenge studies have been used to study a variety of diseases, including influenza, malaria, Dengue fever, and COVID-19, among others. They play a crucial role in advancing medical and scientific knowledge and can accelerate the development of treatments and vaccines.

A human challenge study was mentioned as an alternative clinical trial design at the beginning of the COVID-19 pandemic when the world was desperate to find an effective and safe vaccine. I wrote an article about this: "Human Challenge Study Design for Covid-19 Vaccine Clinical Trials?"

Just this morning, Janssen Announces Promising Antiviral Activity Against Dengue in a Phase 2a Human Challenge Model. The results were from a phase 2a study titled "A Phase 2a, Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics of Repeated Oral Doses of JNJ-64281802 Against Dengue Serotype 3 Infection in a Dengue Human Challenge Model in Healthy Adult Participants" that was posted on clinicaltrials.gov. Unfortunately, the clinical trial registration did not contain any description of the 'Challenge' part (i.e., how the healthy volunteers are exposed to the infectious agents (in this case, the Dengue virus). We will just need to wait for the formal publication of the study to know the details. 

In a paper by Porter et al "A human Phase I/IIa malaria challenge trial of a polyprotein malaria vaccine", the whole details about the human challenge study including the 'challenge' part were discussed. The 'sporozoite challenge' to the healthy volunteers was described below: