Featured Research

from universities, journals, and other organizations

Malaria in pregnant women: Step towards a new vaccine

Date:
March 12, 2010
Source:
CNRS (Délégation Paris Michel-Ange)
Summary:
By managing to express the protein that enables red blood cells infected with the malaria agent Plasmodium falciparum to bind to the placenta and by deciphering its molecular mechanisms, a team of researchers has taken an important first step in the development of a vaccine against pregnancy-associated malaria.

P. falciparum parasitized erythrocytes. The var2CSA protein is colored green.
Credit: Copyright Benoit Gamain, CNRS/Institut Pasteur

By managing to express the protein that enables red blood cells infected with the malaria agent Plasmodium falciparum to bind to the placenta and by deciphering its molecular mechanisms, a team of researchers from CNRS and the Institut Pasteur has taken an important first step in the development of a vaccine against pregnancy-associated malaria.

Their work was published in the journal Proceedings of the National Academy of Sciences.

In endemic areas where malaria is rife, the main victims are children less than three years old. This is because adults acquire, in the course of their lives, an immunity that protects them against the parasite. However, pregnant women, especially during a first pregnancy, have potentially fatal reactions to P. falciparum. The parasites also prevent exchanges of gases and nutrients through the placenta, thereby leading to spontaneous abortions, premature deliveries and newborn babies with too low birth weight, which are serious conditions in countries where infantile mortality is very high in the first year.

Following a bite by an infectious mosquito, the parasite first multiplies in the liver, before entering the bloodstream where it invades the erythrocytes (or red blood cells). The parasite then rapidly modifies the surface of its host erythrocyte with one of the sixty variable proteins of the PfEMP1 (Plasmodium falciparum Erythrocyte Membrane Protein 1) family. These proteins protect the parasite from the host's immune response and enable it to adhere to the host's cells. The severity of pregnancy-associated malaria (PAM) has been associated with the ability of parasitized erythrocytes to bind to a sugar present in the placenta, chondroitin sulfate A (CSA). After several pregnancies, women acquire protective antibodies that block CSA-binding.

One of the potential vaccination strategies for PAM is to recreate this protective immunity, by blocking the binding of parasitized erythrocytes to the placenta. Previous work carried out by the team headed by Benoît Gamain, CNRS researcher at the Unité Bases Génétiques et Moléculaires des Interactions de la Cellule Eucaryote (Institut Pasteur), has shown that one of the proteins of the PfEMP1 family, known as var2CSA, plays an important role in PAM. It is thus the prime target for a vaccine. However, the var2CSA protein shows considerable polymorphism, is very large and has a very complex structure. These characteristics have, until now, prevented researchers from reproducing it in the laboratory and studying it to elucidate its structure and its action mechanisms. Only selected "chunks" of proteins involved in these binding areas, known as domains, have been synthesized.

Gamain and his colleagues have, for the first time, succeeded in producing the entire var2CSA protein for the purpose of studying it. This protein has shown specific, high-affinity binding to CSA, more than a thousand times greater than that of the simple domains synthesized previously. Therefore it is indeed a functional protein, with all the characteristics and functions of the var2CSA protein expressed at the surface of parasitized erythrocytes. Structural studies conducted in collaboration with researchers at EMBL (European Molecular Biology Laboratory) in Grenoble then made it possible to observe the structure of this protein. Var2CSA has a compact rather than a lengthened shape, as was assumed previously, and has a CSA-binding pocket that is most probably created when the protein folds upon itself.

For the researchers, these results constitute a first step in the race to develop vaccinal or therapeutic approaches aimed at protecting women during their first pregnancies as well as their unborn fetuses. Their work, conducted within the European "Premalstruct" consortium headed by Gamain, is now going to focus on the CSA-binding pocket, responsible for the adhesion of parasitized erythrocytes to the cells of the placenta.


Story Source:

The above story is based on materials provided by CNRS (Délégation Paris Michel-Ange). Note: Materials may be edited for content and length.


Journal Reference:

  1. Anand Srivastava, Stéphane Gangnard, Adam Round, Sébastien Dechavanne, Alexandre Juillerat, Bertrand Raynal, Grazyna Faure, Bruno Baron, Stéphanie Ramboarina, Saurabh Kumar Singh, Hassan Belrhali, Patrick England, Anita Lewit-Bentley, Artur Scherf, Graham A. Bentley, Benoît Gamain. Full-length extracellular region of the var2CSA variant of PfEMP1 is required for specific, high-affinity binding to CSA. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1000951107

Cite This Page:

CNRS (Délégation Paris Michel-Ange). "Malaria in pregnant women: Step towards a new vaccine." ScienceDaily. ScienceDaily, 12 March 2010. <www.sciencedaily.com/releases/2010/03/100309112025.htm>.
CNRS (Délégation Paris Michel-Ange). (2010, March 12). Malaria in pregnant women: Step towards a new vaccine. ScienceDaily. Retrieved September 21, 2014 from www.sciencedaily.com/releases/2010/03/100309112025.htm
CNRS (Délégation Paris Michel-Ange). "Malaria in pregnant women: Step towards a new vaccine." ScienceDaily. www.sciencedaily.com/releases/2010/03/100309112025.htm (accessed September 21, 2014).

Share This



More Health & Medicine News

Sunday, September 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) — Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) — Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) — A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) — The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins