The Centre for Infectious Disease Research in Zambia (CIDRZ), through its Enteric Disease and Vaccine Research Unit (EDVRU) has started enrolling participants for a study aimed at (i) assessing protection against rotavirus infection and (ii) to investigate immune correlates of protection following vaccination with a novel trivalent VP8 subunit rotavirus vaccine used alone or in combination with oral rotavirus vaccine used in our national immunisation program.

This study has been fully approved by all local regulatory authorities and is being conducted at Chawama General Hospital in Lusaka, Zambia.

The study will enrol a total of 720 children who will be followed up for study procedures for 5 months. It is funded by the Medical Research Council (UK) https://mrc.ukri.org/  and conducted in collaboration with the  Imperial College  London https://www.imperial.ac.uk/ and PATH https://www.path.org/. The trial has been registered with clinical trials.gov and a description of the trial is available on: https://www.clinicaltrials.gov/. NCT04658914

In 2019, CIDRZ piloted a human infection model which can be used to evaluate new rotavirus vaccines in children by using a routinely administered live attenuated vaccine (Rotarix™) as a challenge agent. Link to the published paper:  https://doi.org/10.1016/j.vaccine.2020.09.023 This work was done in collaboration with partners from Imperial College London with funding from the HICVac Network https://www.hic-vac.org/about-us.

What is Rotavirus and why is it an important public health issue?

Rotavirus associated diarrhoea accounts for approximately 130,000 deaths annually (majority coming from lower middle-income countries), and imposes substantial costs associated with the care of sick children by parents.

The global roll-out of four oral rotavirus WHO prequalified vaccines (i.e., Rotarix™ and RotaTeq™, Rotasil and Rotavac) in over 35 sub-Saharan African countries to date, has demonstrated reduced cases of diarrhoea and deaths associated with rotavirus. Unfortunately, in regions of highest burden of rotavirus diarrhoea, the immunogenicity and efficacy of these vaccines have been reported to be lower than that of high-income countries. The reported estimates for vaccine effectiveness are between 39-61% in Africa compared with over 90% in high-income countries. Postulations for the observed low efficacy border around factors such as elevated maternal antibodies to the infectious agent which stop the live vaccine strain from growing and providing immunity, malnutrition, micro-nutrient deficiencies, persistent exposure to pathogens, or higher prevalence of co-infections in the child’s gut.

Therefore, with this observed phenomenon of suboptimal oral rotavirus vaccines performance in lower income countries, there is an urgent need to (i) develop new vaccines which can perfume better or (ii) explore alternative dosing schedules to improve the performance of existing vaccines.

Using the traditional clinical trials to evaluate performance of new vaccines poses challenges as they often require large sample sizes to answer study questions, and placebo-controlled designs are not ethically possible to conduct. To overcome these barriers, controlled human infection or human infection challenge (HIC) studies are methods that can be used. These studies are increasingly used as tools to not only assess promising candidate vaccines, but also improve understanding of infectious disease immunology. CIDRZ is proud to be a pioneer in this field.