Summary
Zambia is among the countries in sub-Saharan Africa that contribute to the 2.9 million cases and 95,000 deaths resulting from cholera globally. The periodicity of outbreaks cannot be predicted. For example, in the last two decades, Zambia experienced multiple, intermittent outbreaks biannually until 2016. There is inadequate knowledge on long term immunity to cholera after natural infection or vaccination, which, if improved, could help identify ways to improve vaccination strategies.
During the 2016 outbreak, the oral cholera vaccine Shanchol™ (OCV) was introduced into Zambia, with >420,000 doses given to >70% of the target population. In 2021, re-vaccinations are being offered in known hotspot areas to booster immunity against cholera. Here, we propose to collect peripheral mononuclear cells (PBMCs) and serum from previously-vaccinated individuals currently under follow-up and those unvaccinated but exposed to cholera. Memory B Cells (MBCs) from fully or partially-vaccinated (received dose one only) and exposed vaccine naïve individuals will be profiled to determine whether the development of long-term memory to cholera is inferior in naïve individuals’ compared to vaccinated individuals.
Dr. Caroline C Chisenga at Centre for Infectious Disease Research in Zambia (CIDRZ) is investigating Shanchol™-induced long term immunity. Professor Adam Cunningham has experience on how adaptive immunity to pathogens and their component antigens are induced, maintained and function. He will provide support on T and B cell work using PBMCs. Findings will inform global thinking on memory to cholera; when it is lost and potentially when cholera re-vaccination should be implemented in hotspot areas.
Project Outcomes
In Zambia, oral cholera vaccine - Shanchol - is immunogenic. However, we found that generated vibriocidal titres post vaccination wane quickly irrespective of previous vaccination status. Although titres begin to drop by day 14 the levels by day 90 are still insignificantly elevated compared to baseline levels.
Also with the high HIV burden in Zambia, we also found that generally persons living with HIV have lower baseline vibriocidal levels compared to their counterparts despite the rate of waning being the same across all treatment arms i.e. those previously vaccinated with single dose, those vaccinated with 2 doses and those who were not previously vaccinated.
Our conclusion therefore is that if previous exposure to cholera and or vaccination is not sustaining the immune response to oral cholera vaccine, then there is urgent need to understand why this is so if we are to totally eliminate cholera per the Zambia national multisectoral cholera elimination plan. We hope that the system's serology approach would provide more insight and inform vaccine developers.