Developing vaccines to prevent malaria in pregnant women

Ndam, Nicaise Tuikue; Deloron, Philippe

doi:10.1517/14712598.2015.1049595

Cited by 19 publications

(11 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An effective vaccine against placental malaria should induce broadly active and strain-transcending antibodies to block the adhesion of VAR2CSA-expressing parasites to CSA [81,82]. A single cross-sectional study found that women positive for CSA-binding inhibitory antibodies had significantly decreased odds of placental infection, as well as low birthweight and preterm birth [56].…”

Section: Discussionmentioning

confidence: 99%

Pregnancy-specific malarial immunity and risk of malaria in pregnancy and adverse birth outcomes: a systematic review

Cutts

Agius

Lin

et al. 2020

BMC Med

View full text Add to dashboard Cite

Background: In endemic areas, pregnant women are highly susceptible to Plasmodium falciparum malaria characterized by the accumulation of parasitized red blood cells (pRBC) in the placenta. In subsequent pregnancies, women develop protective immunity to pregnancy-associated malaria and this has been hypothesized to be due to the acquisition of antibodies to the parasite variant surface antigen VAR2CSA. In this systematic review we provide the first synthesis of the association between antibodies to pregnancy-specific P. falciparum antigens and pregnancy and birth outcomes. Methods: We conducted a systematic review and meta-analysis of population-based studies (published up to 07 June 2019) of pregnant women living in P. falciparum endemic areas that examined antibody responses to pregnancy-specific P. falciparum antigens and outcomes including placental malaria, low birthweight, preterm birth, peripheral parasitaemia, maternal anaemia, and severe malaria. Results: We searched 6 databases and identified 33 studies (30 from Africa) that met predetermined inclusion and quality criteria: 16 studies contributed estimates in a format enabling inclusion in meta-analysis and 17 were included in narrative form only. Estimates were mostly from cross-sectional data (10 studies) and were heterogeneous in terms of magnitude and direction of effect. Included studies varied in terms of antigens tested, methodology used to measure antibody responses, and epidemiological setting. Antibody responses to pregnancyspecific pRBC and VAR2CSA antigens, measured at delivery, were associated with placental malaria (9 studies) and may therefore represent markers of infection, rather than correlates of protection. Antibody responses to pregnancy-specific pRBC, but not recombinant VAR2CSA antigens, were associated with trends towards protection from low birthweight (5 studies). Conclusions: Whilst antibody responses to several antigens were positively associated with the presence of placental and peripheral infections, this review did not identify evidence that any specific antibody response is associated with protection from pregnancy-associated malaria across multiple populations. Further prospective cohort studies using standardized laboratory methods to examine responses to a broad range of antigens in different epidemiological settings and throughout the gestational period, will be necessary to identify and prioritize pregnancy-specific P. falciparum antigens to advance the development of vaccines and serosurveillance tools targeting pregnant women.

show abstract

Section: Discussionmentioning

confidence: 99%

Pregnancy-specific malarial immunity and risk of malaria in pregnancy and adverse birth outcomes: a systematic review

Cutts

Agius

Lin

et al. 2020

BMC Med

View full text Add to dashboard Cite

show abstract

“…Women in endemic areas urgently need novel interventional methods. In areas of stable transmission, the prevalence and severity of placental malaria diminish with successive pregnancies [ 5 , 6 ] demonstrating that immunity is acquired as a result of natural infection, and supporting the prospects for a vaccine that protects pregnant women and their children from the dire consequences of placental malaria [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical development of placental malaria vaccines and immunoassays harmonization: a workshop report

Chêne

Houard

Nielsen

et al. 2016

Malar J

View full text Add to dashboard Cite

Placental malaria caused by Plasmodium falciparum infection constitutes a major health problem manifesting as severe disease and anaemia in the mother, impaired fetal development, low birth weight or spontaneous abortion. Prevention of placental malaria currently relies on two key strategies that are losing efficacy due to spread of resistance: long-lasting insecticide-treated nets and intermittent preventive treatment during pregnancy. A placental malaria vaccine would be an attractive, cost-effective complement to the existing control tools. Two placental malaria vaccine candidates are currently in Phase Ia/b clinical trials. During two workshops hosted by the European Vaccine Initiative, one in Paris in April 2014 and the other in Brussels in November 2014, the main actors in placental malaria vaccine research discussed the harmonization of clinical development plans and of the immunoassays with a goal to define standards that will allow comparative assessment of different placental malaria vaccine candidates. The recommendations of these workshops should guide researchers and clinicians in the further development of placental malaria vaccines.

show abstract

“…Placental malaria constitutes a large problem in malaria endemic countries and current control strategies based on the administration of repeated curative doses of antimalarial treatment (intermittent preventive treatment during pregnancy, IPTp) during the 2 nd and 3 rd trimester are compromised by development of parasite drug resistance and a general low effective delivery of IPTp programme in sub-Saharan African countries. IPTp also suffers from the inherent problem that the first treatment dose is often given after the initial exposure to malaria and irreversible damage to the placenta has already occurred [ 33 ]. An effective vaccine protecting women against PM infection would circumvent these problems.…”

Section: Discussionmentioning

confidence: 99%

A Novel Virus-Like Particle Based Vaccine Platform Displaying the Placental Malaria Antigen VAR2CSA

et al. 2015

View full text Add to dashboard Cite

Placental malaria caused by Plasmodium falciparum is a major cause of mortality and severe morbidity. Clinical testing of a soluble protein-based vaccine containing the parasite ligand, VAR2CSA, has been initiated. VAR2CSA binds to the human receptor chondroitin sulphate A (CSA) and is responsible for sequestration of Plasmodium falciparum infected erythrocytes in the placenta. It is imperative that a vaccine against malaria in pregnancy, if administered to women before they become pregnant, can induce a strong and long lasting immune response. While most soluble protein-based vaccines have failed during clinical testing, virus-like particle (VLP) based vaccines (e.g., the licensed human papillomavirus vaccines) have demonstrated high efficacy, suggesting that the spatial assembly of the vaccine antigen is a critical parameter for inducing an optimal long-lasting protective immune response. We have developed a VLP vaccine display platform by identifying regions of the HPV16 L1 coat protein where a biotin acceptor site (AviTagTM) can be inserted without compromising VLP-assembly. Subsequent biotinylation of Avi-L1 VLPs allow us to anchor monovalent streptavidin (mSA)-fused proteins to the biotin, thereby obtaining a dense and repetitive VLP-display of the vaccine antigen. The mSA-VAR2CSA antigen was delivered on the Avi-L1 VLP platform and tested in C57BL/6 mice in comparison to two soluble protein-based vaccines consisting of naked VAR2CSA and mSA-VAR2CSA. The mSA-VAR2CSA Avi-L1 VLP and soluble mSA-VAR2CSA vaccines induced higher antibody titers than the soluble naked VAR2CSA vaccine after three immunizations. The VAR2CSA Avi-L1 VLP vaccine induced statistically significantly higher endpoint titres compared to the soluble mSA-VAR2CSA vaccine, after 1st and 2nd immunization; however, this difference was not statistically significant after 3rd immunization. Importantly, the VLP-VAR2CSA induced antibodies were functional in inhibiting the binding of parasites to CSA. This study demonstrates that the described Avi-L1 VLP-platform may serve as a versatile system for facilitating optimal VLP-display of large and complex vaccine antigens.

show abstract

Developing vaccines to prevent malaria in pregnant women

Cited by 19 publications

References 83 publications

Pregnancy-specific malarial immunity and risk of malaria in pregnancy and adverse birth outcomes: a systematic review

Pregnancy-specific malarial immunity and risk of malaria in pregnancy and adverse birth outcomes: a systematic review

Clinical development of placental malaria vaccines and immunoassays harmonization: a workshop report

A Novel Virus-Like Particle Based Vaccine Platform Displaying the Placental Malaria Antigen VAR2CSA

Contact Info

Product

Resources

About