Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B &amp; T cell activity in Beninese primigravidae

Gbédandé, Komi; Fiévet, Nadine; Viwami, Firmine; Ezinmègnon, Sèm; Issifou, Saadou; Chippaux, Jean-Philippe; Dossou, Yannelle; Moutaïrou, Kabirou; Massougbodji, Achille; Ndam, Nicaise Tuikue; Jongh, Willem A. de; Soegaard, Max; Salanti, Ali; Nielsen, Morten A.; Esen, Meral; Mordmüller, Benjamin; Deloron, Philippe; Luty, Adrian J. F.

doi:10.1016/j.vaccine.2017.05.027

Cited by 16 publications

(10 citation statements)

References 28 publications

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“…Although the women studied here had submicroscopic infection and those studied by Cumberland et al had microscopic infection (haemozoin and/or parasites in placental tissue detected by histopathology), in both studies women had chronic infections with unknown timing and/or duration but which were associated with an impaired immune response to vaccination. Furthermore, the frequency of memory B cells with specificity for TT were not modified by P. falciparum infection status in a cohort of primigravid women at the time of delivery . This finding does not support the results obtained in our study.…”

Section: Discussioncontrasting

confidence: 99%

Submicroscopic Plasmodium infection during pregnancy is associated with reduced antibody levels to tetanus toxoid

Álvarez-Larrotta

Agudelo

Duque

et al. 2018

Clinical and Experimental Immunology

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Submicroscopic Plasmodium infections in pregnancy are common in endemic areas, and it is important to understand the impact of these low-level infections. Asymptomatic, chronic infections are advantageous for parasite persistence, particularly in areas where the optimal eco-epidemiological conditions for parasite transmission fluctuate. In chronic infections, the persistence of the antigenic stimulus changes the expression of immune mediators and promotes constant immune regulation, including increases in regulatory T cell populations. These alterations of the immune system could compromise the response to routine vaccination. This study aimed to evaluate the effect of submicroscopic plasmodial infection with P. falciparum and P. vivax during pregnancy on the immune response to the tetanus toxoid vaccine in Colombian women. Expression of different cytokines and mediators of immune regulation and levels of anti-tetanus toxoid (TT) immunoglobulin (Ig)G were quantified in pregnant women with and without submicroscopic plasmodial infection. The anti-TT IgG levels were significantly lower in the infected group compared with the uninfected group. The expression of interferon (IFN)-γ, tumour necrosis factor (TNF) and forkhead box protein 3 (FoxP3) was significantly higher in the infected group, while the expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) and transforming growth factor (TGF)-β was lower in the group of infected. In conclusion, submicroscopic Plasmodium infection altered the development of the immune response to the TT vaccine in Colombian pregnant women. The impact of Plasmodium infections on the immune regulatory pathways warrants further exploration.

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Section: Discussioncontrasting

confidence: 99%

Submicroscopic Plasmodium infection during pregnancy is associated with reduced antibody levels to tetanus toxoid

Álvarez-Larrotta

Agudelo

Duque

et al. 2018

Clinical and Experimental Immunology

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“…This fact, and the identification of the so-called minimal binding domain in VAR2CSA-type PfEMP1 that binds to its cognate receptor, oncofetal chondroitin sulfate, has raised hopes that it may be possible to vaccinate against placental malaria ( 35 – 38 ). Clinical phase Ia/b trials of such vaccines are currently in progress ( 39 , 40 ).…”

Section: Discussionmentioning

confidence: 99%

IgG Responses to the Plasmodium falciparum Antigen VAR2CSA in Colombia Are Restricted to Pregnancy and Are Not Induced by Exposure to Plasmodium vivax

et al. 2018

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“…A total of 200 000 cells per well were incubated for 2 hours at 37°C in a 96-well plate (Falcon 351172) coated the day before with 2 µg/mL CSA (D8428 Sigma-Aldrich) and blocked with 1% immunoglobulin-free bovine serum albumin (A7030 Sigma-Aldrich). Wells were run in triplicate either without plasma or with 4 two-fold dilutions from 1:10 of a pool of plasma from malaria-naive, a pool of plasma samples from malaria-exposed multiparous women from Benin [30], or test plasma in a total volume of 100 µL. Unbound iRBCs were washed away by a pipetting robot (Biomek 2000, Beckman Coulter).…”

Section: Methodsmentioning

confidence: 99%

First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria

Mordmüller

Sulyok

Egger‐Adam

et al. 2019

Clinical Infectious Diseases

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137

105

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Background Malaria in pregnancy has major impacts on mother and child health. To complement existing interventions, such as intermittent preventive treatment and use of impregnated bed nets, we developed a malaria vaccine candidate with the aim of reducing sequestration of asexual “blood-stage” parasites in the placenta, the major virulence mechanism. Methods The vaccine candidate PAMVAC is based on a recombinant fragment of VAR2CSA, the Plasmodium falciparum protein responsible for binding to the placenta via chondroitin sulfate A (CSA). Healthy, adult malaria-naive volunteers were immunized with 3 intramuscular injections of 20 μg (n = 9) or 50 μg (n = 27) PAMVAC, adjuvanted with Alhydrogel or glucopyranosyl lipid adjuvant in stable emulsion (GLA-SE) or in a liposomal formulation with QS21 (GLA-LSQ). Allocation was random and double blind. The vaccine was given every 4 weeks. Volunteers were observed for 6 months following last immunization. Results All PAMVAC formulations were safe and well tolerated. A total of 262 adverse events (AEs) occurred, 94 (10 grade 2 and 2 grade 3) at least possibly related to the vaccine. No serious AEs occurred. Distribution and severity of AEs were similar in all arms. PAMVAC was immunogenic in all participants. PAMVAC-specific antibody levels were highest with PAMVAC-GLA-SE. The antibodies inhibited binding of VAR2CSA expressing P. falciparum-infected erythrocytes to CSA in a standardized functional assay. Conclusions PAMVAC formulated with Alhydrogel or GLA-based adjuvants was safe, well tolerated, and induced functionally active antibodies. Next, PAMVAC will be assessed in women before first pregnancies in an endemic area. Clinical Trials Registration EudraCT 2015-001827-21; ClinicalTrials.gov NCT02647489.

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Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae

Cited by 16 publications

References 28 publications

Submicroscopic Plasmodium infection during pregnancy is associated with reduced antibody levels to tetanus toxoid

Submicroscopic Plasmodium infection during pregnancy is associated with reduced antibody levels to tetanus toxoid

IgG Responses to the Plasmodium falciparum Antigen VAR2CSA in Colombia Are Restricted to Pregnancy and Are Not Induced by Exposure to Plasmodium vivax

First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria

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