Search

Your search keyword '"Issifou, Saadou"' showing total 420 results
Start Over Author "Issifou, Saadou"
420 results on '"Issifou, Saadou"'

2. The Pan African Vivax and Ovale Network (PAVON): Refocusing on Plasmodium vivax, ovale and asymptomatic malaria in sub-Saharan Africa

Author

Quaye, Isaac K., Aleksenko, Larysa, Oeuvray, Claude, Yewhalaw, Delenasaw, Duah, Nancy, Gyan, Ben, Haiyambo, Daniel H., Dongho, Ghyslaine Bruna Djeunang, Torgby, Ruth-Ayanful, Amoah, Linda, Hamid, Mahdi Abdel, Worku, Solomon, Bahiti, Assefa Ashenafi, Pasquale, Harriet Akello, Bitshi, Mimie, Troare, Isidore, Diarra, Amidou, Njunju, Eric, Cisse, Mamoudou, Soulama, Issiaka, Savadogo, Ragnessi Justin, Issifou, Saadou, Niangaly, Amadou, Dembele, Laurent, and Greco, Beatrice

Published
2021
Full Text
View/download PDF

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

Author

Gbédandé, Komi, Fievet, Nadine, Viwami, Firmine, Ezinmegnon, Sem, Issifou, Saadou, Chippaux, Jean-Philippe, Dossou, Yannelle, Moutairou, Kabirou, Massougbodji, Achille, Ndam, Nicaise, de Jongh, Willem Adriaan, Søgaard, T. Max M., Salanti, Ali, Nielsen, Morten A., Esen, Meral, Mordmüller, Benjamin, Deloron, Philippe, and Luty, Adrian J.F.

Published
2017
Full Text
View/download PDF

4. A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children

Author

Ouédraogo, Alphonse, Kargougou, Désiré, Nébié, Issa, Débé, Siaka, Diarra, Amidou, Bougouma, Edith, Hounkpatin, Aurore B., Adegnika, Ayola Akim, Lell, Bertrand, Joanny, Fanny, Honkpehedji, Yabo Josiane, Agobe, Jean Claude Dejon, Esen, Meral, Ajua, Anthony, Asoala, Victor, Anyorigiya, Thomas, Ansah, Nana Akosua, Buwembo, William, Mworozi, Edison, Sekikubo, Musa, Abubakar, Ismaela, Bojang, Kalifa, Noor, Ramadhani, Okech, Brenda, Ejigu, Dawit A., Sirima, Sodiomon B., Mordmüller, Benjamin, Milligan, Paul, Ngoa, Ulysse Ateba, Kironde, Fred, Atuguba, Frank, Tiono, Alfred B., Issifou, Saadou, Kaddumukasa, Mark, Bangre, Oscar, Flach, Clare, Christiansen, Michael, Bang, Peter, Chilengi, Roma, Jepsen, Søren, Kremsner, Peter G., and Theisen, Michael

Published
2016
Full Text
View/download PDF

7. A Simplified Intravenous Artesunate Regimen for Severe Malaria—Reply

Author

Kremsner, Peter Gottfried, Taylor, Terrie, Issifou, Saadou, Kombila, Maryvonne, Chimalizeni, Yamikani, Kawaza, Kondwana, Akotet, Marielle K. Bouyou, Duscha, Mattias, Mordmüller, Benjamin, Kösters, Katrin, Humberg, Alexander, Miller, R. Scott, Weina, Peter, Duparc, Stephan, Möhrle, Jörg, Kun, Jürgen F. J., Planche, Tim, Teja-Isavadharm, Paktiya, Simpson, Julie Anne, Köhler, Carsten, and Krishna, Sanjeev

Published
2012
Full Text
View/download PDF

8. Evaluation of the Safety and Immunogenicity of the RTS,S/AS01 E Malaria Candidate Vaccine When Integrated in the Expanded Program of Immunization

Author

Agnandji, Selidji T., Asante, Kwaku Poku, Lyimo, John, Vekemans, Johan, Soulanoudjingar, Solange S., Owusu, Ruth, Shomari, Mwanajaa, Leach, Amanda, Fernandes, Jose, Dosoo, David, Chikawe, Maria, Issifou, Saadou, Osei-Kwakye, Kingsley, Lievens, Marc, Paricek, Maria, Apanga, Stephen, Mwangoka, Grace, Okissi, Blaise, Kwara, Evans, Minja, Rose, Lange, Jorn, Boahen, Owusu, Kayan, Kingsley, Adjei, George, Chandramohan, Daniel, Jongert, Erik, Demoitié, Marie-Ange, Dubois, Marie-Claude, Carter, Terrel, Vansadia, Preeti, Villafana, Tonya, Sillman, Marla, Savarese, Barbara, Lapierre, Didier, Ballou, William Ripley, Greenwood, Brian, Tanner, Marcel, Cohen, Joe, Kremsner, Peter G., Lell, Bertrand, Owusu-Agyei, Seth, and Abdulla, Salim

Published
2010

17. Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial

Author

Asante, Kwaku Poku, Abdulla, Salim, Agnandji, Selidji, Lyimo, John, Vekemans, Johan, Soulanoudjingar, Solange, Owusu, Ruth, Shomari, Mwanajaa, Leach, Amanda, Jongert, Erik, Salim, Nahya, Fernandes, Jose F, Dosoo, David, Chikawe, Maria, Issifou, Saadou, Osei-Kwakye, Kingsley, Lievens, Marc, Paricek, Maria, Möller, Tina, Apanga, Stephen, Mwangoka, Grace, Dubois, Marie-Claude, Madi, Tigani, Kwara, Evans, Minja, Rose, Hounkpatin, Aurore B, Boahen, Owusu, Kayan, Kingsley, Adjei, George, Chandramohan, Daniel, Carter, Terrell, Vansadia, Preeti, Sillman, Marla, Savarese, Barbara, Loucq, Christian, Lapierre, Didier, Greenwood, Brian, Cohen, Joe, Kremsner, Peter, Owusu-Agyei, Seth, Tanner, Marcel, and Lell, Bertrand

Published
2011
Full Text
View/download PDF

18. Intermittent Preventive Treatment against Malaria in Infants in Gabon: A Randomized, Double-Blind, Placebo-Controlled Trial

Author

Grobusch, Martin P., Lell, Bertrand, Schwarz, Norbert G., Gabor, Julian, Dörnemann, Jenny, Pötschke, Marc, Oyakhirome, Sunny, Kiessling, Georg C., Necek, Magdalena, Längin, Matthias U., Klouwenberg, Peter Klein, Klöpfer, Anna, Naumann, Benjamin, Altun, Handan, Agnandji, Selidji T., Goesch, Julia, Decker, Marieluise, Ospina Salazar, Carmen L., Supan, Christian, Kombila, Davy U., Borchert, Lea, Köster, Kai B., Pongratz, Peter, Adegnika, Akim A., von Glasenapp, Isabelle, Issifou, Saadou, and Kremsner, Peter G.

Published
2007
Full Text
View/download PDF

20. Clinical and Parasitological Characteristics of Puerperal Malaria

Author

Ramharter, Michael, Grobusch, Martin P., KieBling, Georg, Adegnika, Ayola A., Moller, Ulrike, Agnandji, Selidji T. M., Kramer, Martin, Schwarz, Norbert, Kun, Jürgen F. J., Oyakhirome, Sunny, Issifou, Saadou, Borrmann, Steffen, Lell, Bertrand, Mordmüller, Benjamin, and Kremsner, Peter G.

Published
2005

23. Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials

Author

Aponte, John J, Schellenberg, David, Egan, Andrea, Breckenridge, Alasdair, Carneiro, Ilona, Critchley, Julia, Danquah, Ina, Dodoo, Alexander, Kobbe, Robin, Lell, Bertrand, May, Jürgen, Premji, Zul, Sanz, Sergi, Sevene, Esperanza, Soulaymani-Becheikh, Rachida, Winstanley, Peter, Adjei, Samuel, Anemana, Sylvester, Chandramohan, Daniel, Issifou, Saadou, Mockenhaupt, Frank, Owusu-Agyei, Seth, Greenwood, Brian, Grobusch, Martin P, Kremsner, Peter G, Macete, Eusebio, Mshinda, Hassan, Newman, Robert D, Slutsker, Laurence, Tanner, Marcel, Alonso, Pedro, and Menendez, Clara

Published
2009
Full Text
View/download PDF

24. Experimental Transmission of Plasmodium malariae to Anopheles gambiae

Author

Pinilla, Yudi T, Boussougou-Sambe, Stravensky T, Gräßle, Sarah, Ngossanga, Barclaye, Doumba-Ndalembouly, Ange G, Weierich, Andrea, Bingoulou, Gedeon, Malinga, Emma G, Nguiffo-Nguete, Daniel, Ntoumi, Francine, Djogbénou, Luc, Issifou, Saadou, Wondji, Charles, Adegnika, Ayola A, and Borrmann, Steffen

Subjects
qx_135, parasitic diseases, qx_515, wc_750
Abstract

Our current knowledge of the clinical burden, biology, and\ud transmission of Plasmodium malariae is extremely scarce. To\ud start addressing some of those questions, we experimentally\ud infected Anopheles gambiae mosquitoes with fresh P. malariae\ud isolates obtained from asymptomatic individuals in Lambaréné,\ud Gabon. The proportion of mosquitoes infected via direct membrane\ud feeding assay with either P. malariae monoinfections\ud (16% [19 of 121]) or coinfections (28% [31 of 112]) was higher\ud after serum replacement than in parallel groups without serum\ud replacement (4% [4 of 102] and 4% [2 of 45], respectively;\ud P < .01). Our results show that isolates from asymptomatic\ud carriers can be used for experimental studies of P. malariae\ud transmission.

Published
2021

31. Effect of immune regulatory pathways after immunization with GMZ2 malaria vaccine candidate in healthy lifelong malaria-exposed adults

Author

Nouatin, Odilon, Ateba Ngoa, Ulysse, Ibáñez, Javier, Dejon-Agobe, Jean Claude, Mordmüller, Benjamin, Edoa, Jean Ronald, Mougeni, Fabrice, Brückner, Sina, Bouyoukou Hounkpatin, Aurore, Esen, Meral, Theisen, Michael, Moutairou, Kabirou, Hoffman, Stephen L, Issifou, Saadou, Luty, Adrian J F, Loembe, Marguerite M, Agnandji, Selidji Todagbé, Lell, Bertrand, Kremsner, Peter G, Adegnika, Ayôla Akim, Nouatin, Odilon, Ateba Ngoa, Ulysse, Ibáñez, Javier, Dejon-Agobe, Jean Claude, Mordmüller, Benjamin, Edoa, Jean Ronald, Mougeni, Fabrice, Brückner, Sina, Bouyoukou Hounkpatin, Aurore, Esen, Meral, Theisen, Michael, Moutairou, Kabirou, Hoffman, Stephen L, Issifou, Saadou, Luty, Adrian J F, Loembe, Marguerite M, Agnandji, Selidji Todagbé, Lell, Bertrand, Kremsner, Peter G, and Adegnika, Ayôla Akim

Abstract

BACKGROUND: Despite appreciable immunogenicity in malaria-naive populations, many candidate malaria vaccines are considerably less immunogenic in malaria-exposed populations. This could reflect induction of immune regulatory mechanisms involving Human Leukocyte Antigen G (HLA-G), regulatory T (Treg), and regulatory B (Breg) cells. Here, we addressed the question whether there is correlation between these immune regulatory pathways and both plasmablast frequencies and vaccine-specific IgG concentrations.METHODS: Fifty Gabonese adults with lifelong exposure to Plasmodium spp were randomized to receive three doses of either 30 µg or 100 µg GMZ2-CAF01, or 100 µg GMZ2-alum, or control vaccine (rabies vaccine) at 4-week intervals. Only plasma and peripheral blood mononuclear cells isolated from blood samples collected before (D0) and 28 days after the third vaccination (D84) of 35 participants were used to measure sHLA-G levels and anti-GMZ2 IgG concentrations, and to quantify Treg, Breg and plasmablast cells. Vaccine efficacy was assessed using controlled human malaria infection (CHMI) by direct venous inoculation of Plasmodium falciparum sporozoites (PfSPZ Challenge).RESULTS: The sHLA-G concentration increased from D0 to D84 in all GMZ2 vaccinated participants and in the control group, whereas Treg frequencies increased only in those receiving 30 µg or 100 µg GMZ2-CAF01. The sHLA-G level on D84 was associated with a decrease of the anti-GMZ2 IgG concentration, whereas Treg frequencies on D0 or on D84, and Breg frequency on D84 were associated with lower plasmablast frequencies. Importantly, having a D84:D0 ratio of sHLA-G above the median was associated with an increased risk of P. falciparum infection after sporozoites injection.CONCLUSION: Regulatory immune responses are induced following immunization. Stronger sHLA-G and Treg immune responses may suppress vaccine induced immune responses, and the magnitude of the sHLA-G response increased the

Published
2020

33. Artesunate-clindamycin versus quinine-clindamycin in the treatment of Plasmodium falciparum malaria: a randomized controlled trial

Author

Ramharter, Michael, Oyakhirome, Sunny, Klouwenberg, Peter Klein, Adegnika, Ayola A., Agnandji, Selidji T., Missinou, Michel A., Matsiegui, Pierre-Blaise, Mordmuller, Benjamin, Borrmann, Steffen, Kun, Jurgen F., Lell, Bertrand, Krishna, Sanjeev, Graninger, Wolfgang, Issifou, Saadou, and Kremsner, Peter G.

Subjects
Quinine -- Dosage and administration, Malaria -- Drug therapy, Clindamycin -- Dosage and administration, Health, Health care industry
Published
2005

36. Effect of immune regulatory pathways after immunization with GMZ2 malaria vaccine candidate in healthy lifelong malaria-exposed adults

Author

Nouatin, Odilon, primary, Ateba Ngoa, Ulysse, additional, Ibáñez, Javier, additional, Dejon-Agobe, Jean Claude, additional, Mordmüller, Benjamin, additional, Edoa, Jean Ronald, additional, Mougeni, Fabrice, additional, Brückner, Sina, additional, Bouyoukou Hounkpatin, Aurore, additional, Esen, Meral, additional, Theisen, Michael, additional, Moutairou, Kabirou, additional, Hoffman, Stephen L., additional, Issifou, Saadou, additional, Luty, Adrian J.F., additional, Loembe, Marguerite M., additional, Agnandji, Selidji Todagbé, additional, Lell, Bertrand, additional, Kremsner, Peter G., additional, and Adegnika, Ayôla Akim, additional

Published
2020
Full Text
View/download PDF

37. Assessment of the anti-HBs antibody response in Beninese infants following 4 doses of HBV vaccine, including administration at birth, compared to the standard 3 doses regime; a cross-sectional survey

Author

Accrombessi, Manfred, primary, Adetola, Crepin Victor, additional, Bacharou, Salwane, additional, Dossou, Yannelle, additional, Avokpaho, Euripide, additional, Yakoubou, Annatou, additional, Koumakpai-Adeothy, Sikiratou, additional, Lozes, Evelyne, additional, and Issifou, Saadou, additional

Published
2020
Full Text
View/download PDF

39. Evaluation of the safety and immunogenicity of the RTS,S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization

Author

Agnandji, Selidji T., Asante, Kwaku Poku, Lyimo, John, Vekemans, Johan, Soulanoudjingar, Solange S., Owusu, Ruth, Shomari, Mwanajaa, Leach, Amanda, Fernandes, Jose, Dosoo, David, Chikawe, Maria, Issifou, Saadou, Osei-Kwakye, Kingsley, Lievens, Marc, Paricek, Maria, Apanga, Stephen, Mwangoka, Grace, Okissi, Blaise, Kwara, Evans, Minja, Rose, Lange, Jorn, Boahen, Owusu, Kayan, Kingsley, Adjei, George, Chandramohan, Daniel, Jongert, Erik, Demoitie, Marie-Ange, Dubois, Marie-Claude, Carter, Terrel, Vansadia, Preeti, Villafana, Tonya, Sillman, Marla, Savarese, Barbara, Lapierre, Didier, Ballou, William Ripley, Greenwood, Brian, Tanner, Marcel, Cohen, Joe, Kremsner, Peter G., Lell, Bertrand, Owusu-Agyei, Seth, and Abdulla, Salim

Subjects
Immunization -- Usage, Immunization -- Health aspects, Malaria -- Prevention, Malaria vaccine -- Usage, Malaria vaccine -- Health aspects, Malaria vaccine -- Safety and security measures, Health
Published
2010

40. Recognition of Plasmodium falciparum mature gametocyte-infected erythrocytes by antibodies of semi-immune adults and malaria-exposed children from Gabon

Author

Gebru, Tamirat, Ajua, Anthony, Theisen, Michael, Esen, Meral, Ngoa, Ulysse Ateba, Issifou, Saadou, Adegnika, Ayola Akim, Kremsner, Peter G, Mordmüller, Benjamin, and Held, Jana

Subjects
Adult, Male, Erythrocytes, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Immune modulation, Plasmodium falciparum, Antibodies, Protozoan, lcsh:Infectious and parasitic diseases, Young Adult, Helminths, Malaria Vaccines, parasitic diseases, Humans, lcsh:RC109-216, Gabon, Malaria, Falciparum, Trichuris trichiura, Ascaris lumbricoides, Clinical isolates, Research, Infant, Newborn, Infant, Flow Cytometry, Malaria, GMZ2, Child, Preschool, Female, Transmission blocking
Abstract

BACKGROUND: Transmission of malaria from man to mosquito depends on the presence of gametocytes, the sexual stage of Plasmodium parasites in the infected host. Naturally acquired antibodies against gametocytes exist and may play a role in controlling transmission by limiting the gametocyte development in the circulation or by interrupting gamete development and fertilization in the mosquito following ingestion. So far, most studies on antibody responses to sexual stage antigens have focused on a subset of gametocyte-surface antigens, even though inhibitory Ab responses to other gametocyte antigens might also play a role in controlling gametocyte density and fertility. Limited information is available on natural antibody response to the surfaces of gametocyte-infected erythrocytes.METHODS: Ab responses to surface antigens of erythrocytes infected by in vitro differentiated Plasmodium falciparum mature gametocytes were investigated in sera of semi-immune adults and malaria-exposed children. In addition, the effect of immunization with GMZ2, a blood stage malaria vaccine candidate, and the effect of intestinal helminth infection on the development of immunity to gametocytes of P. falciparum was evaluated in malaria-exposed children and adults from Gabon. Serum samples from two Phase I clinical trials conducted in Gabon were analysed by microscopic and flow-cytometric immunofluorescence assay.RESULTS: Adults had a higher Ab response compared to children. Ab reactivity was significantly higher after fixation and permeabilization of parasitized erythrocytes. Following vaccination with the malaria vaccine candidate GMZ2, anti-gametocyte Ab concentration decreased in adults compared to baseline. Ab response to whole asexual stage antigens had a significant but weak positive correlation to anti-gametocyte Ab responses in adults, but not in children. Children infected with Ascaris lumbricoides had a significantly higher anti-gametocyte Ab response compared to non-infected children.CONCLUSION: The current data suggest that antigens exposed on the gametocyte-infected red blood cells are recognized by serum antibodies from malaria-exposed children and semi-immune adults. This anti-gametocyte immune response may be influenced by natural exposure and vaccination. Modulation of the natural immune response to gametocytes by co-infecting parasites should be investigated further and may have an important impact on malaria control strategies.

Published
2017
Full Text
View/download PDF

42. Intramuscular artesunate for severe malaria in African children: a multicenter randomized controlled trial

Author

Kremsner, Peter G., Adegnika, Akim A., Hounkpatin, Aurore B., Zinsou, Jeannot F., Taylor, Terrie E., Chimalizeni, Yamikani, Liomba, Alice, Kombila, Maryvonne, Bouyou-Akotet, Marielle K., Mboumba, Denise P. Mawili, Agbenyega, Tsiri, Ansong, Daniel, Sylverken, Justice, Ogutu, Bernhards R., Otieno, Godfrey A., Wangwe, Anne, Bojang, Kalifa A., Okomo, Uduak, Sanya- Isijola, Frank, Newton, Charles R., Njuguna, Patricia, Kazungu, Michael, Kerb, Reinhold, Geditz, Mirjam, Schwab, Matthias, Velavan, Thirumalaisamy P., Nguetse, Christian, Kohler, Carsten, Issifou, Saadou, Bolte, Stefanie, Engleitner, Thomas, Mordmuller, Benjamin, and Krishna, Sanjeev

Subjects
Children -- Diseases, Malaria -- Drug therapy, Biological sciences
Abstract

Background Current artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%). Methods and Findings This randomized controlled trial included children (0.5-10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0,12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0,24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with >99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan-Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7g/dl 7 d or more after admission. The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i. m. arm, 265/338 (78%) children had a >99% reduction in parasitemia at 24 h compared to 263/331 (79%) receiving the five-dose i.m. regimen, showing non-inferiority of the simplified three-dose regimen to the conventional five-dose regimen (95% CI -7,5; p = 0.02). In the three-dose i.v. arm, 246/333 (74%) children had ≥ 99% reduction in parasitemia at 24 h; hence, non-inferiority of this regimen to the five-dose control regimen was not shown (95% CI -12,1; p = 0.24). Delayed parasite clearance was associated with the [sup.N86Y]Pfmdr1 genotype. In a post hoc analysis, 192/885 (22%) children developed delayed anemia, an adverse event associated with increased leukocyte counts. There was no observed difference in delayed anemia between treatment arms. A potential limitation of the study is its open-label design, although the primary outcome measures were assessed in a blinded manner. Conclusions A simplified three-dose i.m. regimen for severe malaria in African children is non-inferior to the more complex WHO-recommended regimen. Parenteral ARS is associated with a risk of delayed anemia in African children. Trial registration Pan African Clinical Trials Registry PACTR201102000277177, Introduction Studies to optimize artesunate (ARS) treatment regimens in malaria have been surprisingly sparse, given that ARS is now established as the treatment of choice for severe malaria in both [...]

Published
2016
Full Text
View/download PDF

45. First-in-human, randomized, double-blind clinical trial of differentially adjuvanted PAMVAC, a vaccine candidate to prevent pregnancy-associated malaria

Author

Mordmüller, Benjamin, Sulyok, Mihály, Egger-Adam, Diane, Resende, Mafalda, de Jongh, Willem A, Jensen, Mette H., Smedegaard, Helle Holm, Ditlev, Sisse B, Soegaard, Max, Poulsen, Lars, Dyring, Charlotte, Calle, Carlos Lamsfus, Knoblich, Annette, Ibáñez, Javier, Esen, Meral, Deloron, Philippe, Ndam, Nicaise, Issifou, Saadou, Houard, Sophie, Howard, Randall F, Reed, Steven G, Leroy, Odile, Luty, Adrian J F, Theander, Thor G, Kremsner, Peter G, Salanti, Ali, Nielsen, Morten A, Mordmüller, Benjamin, Sulyok, Mihály, Egger-Adam, Diane, Resende, Mafalda, de Jongh, Willem A, Jensen, Mette H., Smedegaard, Helle Holm, Ditlev, Sisse B, Soegaard, Max, Poulsen, Lars, Dyring, Charlotte, Calle, Carlos Lamsfus, Knoblich, Annette, Ibáñez, Javier, Esen, Meral, Deloron, Philippe, Ndam, Nicaise, Issifou, Saadou, Houard, Sophie, Howard, Randall F, Reed, Steven G, Leroy, Odile, Luty, Adrian J F, Theander, Thor G, Kremsner, Peter G, Salanti, Ali, and Nielsen, Morten A

Abstract

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.

Published
2019

48. A flow cytometry-based workflow for detection and quantification of anti-plasmodial antibodies in vaccinated and naturally exposed individuals

Author

Ajua Anthony, Engleitner Thomas, Esen Meral, Theisen Michael, Issifou Saadou, and Mordmüller Benjamin

Subjects
Malaria, Flow cytometry-based IFA, Algorithmic data analysis, Anti-malarial antibodies, Human serum, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Antibodies play a central role in naturally acquired immunity against Plasmodium falciparum. Current assays to detect anti-plasmodial antibodies against native antigens within their cellular context are prone to bias and cannot be automated, although they provide important information about natural exposure and vaccine immunogenicity. A novel, cytometry-based workflow for quantitative detection of anti-plasmodial antibodies in human serum is presented. Methods Fixed red blood cells (RBCs), infected with late stages of P. falciparum were utilized to detect malaria-specific antibodies by flow cytometry with subsequent automated data analysis. Available methods for data-driven analysis of cytometry data were assessed and a new overlap subtraction algorithm (OSA) based on open source software was developed. The complete workflow was evaluated using sera from two GMZ2 malaria vaccine trials in semi-immune adults and pre-school children residing in a malaria endemic area. Results Fixation, permeabilization, and staining of infected RBCs were adapted for best operation in flow cytometry. As asexual blood-stage vaccine candidates are designed to induce antibody patterns similar to those in semi-immune adults, serial dilutions of sera from heavily exposed individuals were compared to naïve controls to determine optimal antibody dilutions. To eliminate investigator effects introduced by manual gating, a non-biased algorithm (OSA) for data-driven gating was developed. OSA-derived results correlated well with those obtained by manual gating (r between 0.79 and 0.99) and outperformed other model-driven gating methods. Bland-Altman plots confirmed the agreement of manual gating and OSA-derived results. A 1.33-fold increase (p=0.003) in the number of positive cells after vaccination in a subgroup of pre-school children vaccinated with 100 μg GMZ2 was present and in vaccinated adults from the same region we measured a baseline-corrected 1.23-fold, vaccine-induced increase in mean fluorescence intensity of positive cells (p=0.03). Conclusions The current workflow advances detection and quantification of anti-plasmodial antibodies through improvement of a bias-prone, low-throughput to an unbiased, semi-automated, scalable method. In conclusion, this work presents a novel method for immunofluorescence assays in malaria research.

Published
2012
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results