Understanding How Plasmodium falciparum Binds to the Placenta and Produces Pathology Provides a Rationale for Pregnancy-Associated Malaria Vaccine Development

Abstract

By adulthood repeated exposure to Plasmodium falciparum, the causative agent of the most severe form of malaria in humans, can induce semi-immunity to clinical infection. During pregnancy, however, there is a striking recurrence of severe disease, a syndrome described as pregnancy-associated malaria (PAM). This is caused by P. falciparum-infected erythrocytes binding to receptors on the placental endothelium that are expressed uniquely during pregnancy. This subset of parasites binds by virtue of expressing a cell surface antigen that is the ligand for the corresponding endothelial receptor, thereby providing a selective pressure for its clonal expansion. The antigen also triggers a protective antibody-mediated immune response. With subsequent pregnancies and further exposure to these variant parasites, antibodies develop earlier and women may experience milder infections. Women with PAM exhibit more severe malaria infections than do non-gravid women, with 2,500-10,000 deaths each year due to haemolytic anaemia. PAM also has a detrimental effect on the foetus, increasing the risk of low birth weight, which causes 60,000-200,000 infant deaths annually in sub-Saharan Africa. Current research aims to produce a vaccine to stimulate development of antibodies which would be protective against infection with wild-type parasites. This is hampered by significant diversity in variant surface antigens and available vaccine candidates may only protect women living in malaria-endemic areas. While placental-parasite interactions are not sufficiently understood, incremental progress is being made towards producing an effective vaccine. This review focuses on the molecular structures involved in binding to consider the prospects for a vaccine mimicking naturally-acquired immunity to PAM.

Therapies to Combat Co-Infection of HIV and Malaria during Pregnancy in Sub-Saharan Africa

“…In regard to pregnancy, the natural build-up of immunity over successive pregnancies due to production of antibodies that recognize placental parasites and which prevent their binding to the placenta suggest the feasibility of developing a pregnancy-associated vaccine [25,75]. Serological studies indicate that a single or finite number of antigens may be required in order to elicit protective immunity based on the production of parasite-specific antibodies [76].…”

Progress on the Path to a Licensed Vaccine Against Plasmodium Falciparum Malaria

“…[34] It should also reproduce, or better still, improve upon naturally acquired immunity and be long-term without necessary boosters or interference from other vaccines. [35] Finally, it should be inexpensive to manufacture and purchase. Unfortunately, malaria vaccines are unlikely to fulfil some of this 'wish list' of properties.…”

“…Instead, it is more probable that they will be moderately effective, confer short-term immunity and be difficult and expensive to make. [34][35][36] mAlArIA vAccInes -current stAte Due to the shortfall in effectiveness of other malaria control measures, increased attention on vaccines led to the formation in 1999 of the PATH Malaria Vaccine Initiative (MVI), a non-government organization (NGO) based in Washington DC, USA, which facilitates accelerated testing of malaria vaccines. [37] There are currently around 63 documented malaria vaccine candidates, including 41 in preclinical and clinical trials.…”

Prevalence, risk factors, and antimalarial resistance patterns of falciparum plasmodiasis among pregnant women in Kaduna metropolis, Nigeria

“…It has been estimated that about 26% of maternal anemia is due to malaria. In Africa, it was reported that severe anemia as a result of falciparum malaria is responsible for approximately 10,000 maternal deaths per annum [ 2 ]. Infants with congenital malaria also experience devastating effects from the infection.…”