Needle-Free intervention as natural vaccine against malaria

A study published today in the journal Science Translation Medicine propose that preventive treatment with affordable and safe antibiotics in people living in areas with intense malaria transmission has the potential to act as a "needle-free" natural vaccine against malaria and may likely provide an additional valuable tool for controlling and/or eliminating malaria in resource-poor settings.

The research, conducted by a multinational team of researchers from the Heidelberg University School of Medicine and the Max Planck Institute for Infection Biology, Germany, London School of Tropical Medicine and Hygiene, UK and the KEMRI-Wellcome Trust Research Programme, Kenya, found that healthy mice infected with malaria parasites during administration of preventative antibiotics developed a vaccine-like immunity against re-infection.

Approximately, half the world’s population is at risk of malaria and about one million people (mainly children living in sub-Saharan Africa) die each year from malaria, a mosquito-borne parasitic disease. Malaria parasites are transmitted to people through the bite of an infected Anopheles mosquito. Only an estimated 10 to 100 parasites per mosquito bite invade the liver where they replicate. About a week after infection, tens of thousands of parasites are released into the bloodstream where they are responsible for malaria’s recurring fevers and cause life-threatening complications.

In this study in mice, the researchers showed that the antibiotics caused a cellular defect in malaria parasites during their passage into the liver of the infected host. This action did not prevent parasite replication in the liver but blocked the malaria parasite’s fatal conversion to the disease causing blood stage. The very late arrest of parasites in the liver allowed the immune system to mount a robust defense against subsequent infections, akin to experimental whole organism vaccine strategies using attenuated parasites.

As already established, antibiotics, especially in combination with other anti-malarial drugs, are safe and affordable drugs against an acute malaria infection. The novel concept is to take advantage of the immunological benefit of antibiotic prophylaxis in areas of moderate to high malaria transmission. In these settings, humans are continuously exposed to new malaria infections delivered by natural mosquito transmission that can be prevented by antibiotics. In the liver, a surplus of parasites presented to the immune system results in robust induction of memory immune responses that can recognize and destroy future malaria infections in the liver, when antibiotics are no longer taken.

Dr Steffen Borrman co-author on the paper says that ‘this proof-of-principle study attempts to bridge a gap between basic malaria research and a rapid translation to a potential application in malaria-endemic countries. An important follow-up of this work is the validation of our experimental approach by clinical trials in humans. If successful, periodic administration of antibiotics, preferably in drug combinations, in high-risk population groups, particularly young, non-immune children, may provide an additional valuable tool for controlling and/or eliminating malaria in resource-poor settings.’

Contact
Juliette Mutheu
Science Communications
KEMRI-Wellcome Trust Research Programme,
T: +254 (0)20 2720163; 2715160
E: jmutheunairobi [dot] kemri-wellcome [dot] org

Images

Anopheles Mosquito (Volker Brinkmann).

This electron micrograph shows a female Anopheles stephensi mosquito, a natural 
vector for Plasmodium parasites. Parasites, termed sporozoites, are injected into the 
host skin during the probing phase in search for a blood capillary. Antibiotic prophylaxis 
arrests the parasite life cycle only after maturation of parasite daughter cells and is a 
surrogate needle-free malaria immunization strategy that takes advantage of natural 
mosquito-born sporozoite injection.

Author contacts for commentary

Dr Steffen Borrmann: sborrmannkilifi [dot] kemri-wellcome [dot] org  (+254 723 487 242)

Impartial contacts for commentary

Dominique Mazier (dominique [dot] mazierupmc [dot] fr)

Robert Sauerwein (R [dot] Sauerweinmmb [dot] umcn [dot] nl)

Laurent Renia (renia_laurentimmunol [dot] a-star [dot] edu [dot] sg)

Notes for editors

1. Friesen, J., Silvie, O., Putrianti, E. D., Hafalla, J. C., Matuschewski, R. K., and S. Borrmann (2010). Natural immunization against malaria: Causal prophylaxis with antibiotics. Science Translational Medicine, 2, 40ra49.

For requests on the paper please email the Science Press Package Team at scipakaaas [dot] org. 

2. The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. http://www.wellcome.ac.uk

3. The Kenya Medical Research Institute (KEMRI) is a Kenya government parastatal with the responsibility for health research to improve the health of Kenyans. It is one of the most well developed national research institutes in Africa with a network of centres across Kenya such as the Centre of Geographic Medicine Research Coast that is home to the KEMRI-Wellcome Trust Research Programme. The programme formally established in 1989, is a partnership between KEMRI, Oxford University and the Wellcome Trust. It conducts basic, epidemiological and clinical research in parallel, with results feeding directly into local and international health policy, and aims to expand the country's capacity to conduct multidisciplinary research that is strong, sustainable and internationally competitive. www.kemri-wellcome.org

2. Heidelberg University School of Medicine. With close links between research labs and hospital wards, swift implementation of newly acquired knowledge from clinical studies, practically oriented modern teaching methods and systematic encouragement for young researchers, the Faculty of Medicine Heidelberg is one of the leading institutions for medical research and training in Germany. One of the four original Faculties of the University in 1386, it rose to new heights in the 19th and 20th centuries with the presence of internationally renowned physicians like Hermann von Helmholtz, Vinzenz Czerny and Ludolf von Krehl. In 1910 and 1922 respectively, Albrecht Kossel and Otto Meyerhof were awarded the Nobel Prize for medicine, a distinction also accorded more recently to Bert Sakmann in 1991 and Harald zur Hausen in 2008. http://www.uni-heidelberg.de/university/welcome/medics-ma.html

3. Max Planck Institute for Infection Biology Max Planck Institute for Infection Biology (MPIIB) being one of currently 78 institutes run by the Max Planck Society for the Advancement of Science, a German non-profit, charitable public body, the institute is among Europe's centres of excellence committed to biological research in the field of infectious diseases. It uses multi-disciplinary research approaches to infection biology, comprising concepts and methodologies of molecular genetics, immunology, cell biology, molecular epidemiology, clinical research and structural chemistry. It particularly aims at a better understanding of the biology of intracellular pathogens and the identification and structural/functional characterisation of pathogen molecules essential for intracellular survival as well as for virulence and persistence. It promotes the applications of its research towards paving the way for the design of rational measures to control infectious diseases. Development and improvement of vaccines and anti-infectives are major goals. http://www.mpiib-berlin.mpg.de/