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Agnandji S.T.,Medical Research Unit | Agnandji S.T.,University of Tubingen | Fendel R.,Medical Research Unit | Fendel R.,University of Tubingen | And 31 more authors.
PLoS ONE | Year: 2011

The recombinant circumsporozoite protein (CS) based vaccine, RTS,S, confers protection against Plasmodium falciparum infection in controlled challenge trials and in field studies. The RTS,S recombinant antigen has been formulated with two adjuvant systems, AS01 and AS02, which have both been shown to induce strong specific antibody responses and CD4 T cell responses in adults. As infants and young children are particularly susceptible to malaria infection and constitute the main target population for a malaria vaccine, we have evaluated the induction of adaptive immune responses in young children living in malaria endemic regions following vaccination with RTS,S/AS01E and RTS,S/AS02D. Our data show that a CS-specific memory B cell response is induced one month after the second and third vaccine dose and that CS-specific antibodies and memory B cells persist up to 12 months after the last vaccine injection. Both formulations also induced low but significant amounts of CS-specific IL-2+ CD4+ T cells one month after the second and third vaccine dose, upon short-term in vitro stimulation of whole blood cells with peptides covering the entire CS derived sequence in RTS,S. These results provide evidence that both RTS,S/AS01E and RTS,S/AS02D induced adaptive immune responses including antibodies, circulating memory B cells and CD4+ T cells directed against P. falciparum CS protein. Trial Registration: ClinicalTrials.gov NCT00307021. © 2011 Agnandji et al.

Ansong D.,Kwame Nkrumah University Of Science And Technology | Asante K.P.,Kintampo Health Research Center | Asante K.P.,London School of Hygiene and Tropical Medicine | Vekemans J.,Glaxosmithkline | And 27 more authors.
PLoS ONE | Year: 2011

Background: The Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against malaria in sub-Saharan Africa. RTS,S formulated with the liposome based adjuvant AS01E or the oil-in-water based adjuvant AS02D induces P. falciparum circumsporozoite (CSP) antigen-specific antibody and T cell responses which have been associated with protection in the experimental malaria challenge model in adults. Methods: This study was designed to evaluate the safety and immunogenicity induced over a 19 month period by three vaccination schedules (0,1-, 0,1,2- and 0,1,7-month) of RTS,S/AS01E and RTS,S/AS02D in children aged 5-17 months in two research centers in Ghana. Control Rabies vaccine using the 0,1,2-month schedule was used in one of two study sites. Results: Whole blood antigen stimulation followed by intra-cellular cytokine staining showed RTS,S/AS01E induced CSP specific CD4 T cells producing IL-2, TNF-α, and IFN-γ. Higher T cell responses were induced by a 0,1,7-month immunization schedule as compared with a 0,1- or 0,1,2-month schedule. RTS,S/AS01E induced higher CD4 T cell responses as compared to RTS,S/AS02D when given on a 0,1,7-month schedule. Conclusions: These findings support further Phase III evaluation of RTS,S/AS01E. The role of immune effectors and immunization schedules on vaccine protection are currently under evaluation. Trial Registration: ClinicalTrials.gov NCT00360230. © 2011 Ansong et al.

Ranaivomanana P.,Institute Pasteur Of Madagascar | Raharimanga V.,Institute Pasteur Of Madagascar | Dubois P.M.,Immunovacc Consulting | Richard V.,Institute Pasteur Of Madagascar | And 2 more authors.
PLoS ONE | Year: 2015

Objective Although the Bacillus Calmette-Guérin vaccine (BCG) protects young children against serious forms of TB, protection against pulmonary TB is variable. We assessed BCG vaccineinduced cellular immune responses and determined for how long they could be detected during childhood in Antananarivo, Madagascar. Methods We assessed BCG vaccine-induced cellular immune responses by TST and IGRA (inhouse ELISPOT assay) using BCG and PPD as stimulation antigen, and compared results between vaccinated and non-vaccinated schoolchildren of two age groups, 6-7 and 13-14 years old. Results Three hundred and sixty-three healthy schoolchildren were enrolled. TST was performed on 351 children and IGRA on 142. A high proportion (66%; 229/343) of the children had no TST reactivity (induration size 0 mm). TST-positive responses ( ≥ 15 mm) were more prevalent among 13-14 year-old (31.7%) than 6-7 year old (16.5%) children, both in the non-vaccinated (43% vs. 9%, p<0.001) and vaccinated (29% vs. 13%, p=0.002) subgroups. There were no significant differences in TST responses between vaccinated and non-vaccinated children in either of the age groups. The IGRA response to BCG and to PPD stimulation was not significantly different according to BCG vaccination record or to age group. A high rate (15.5%; 22/142) of indeterminate IGRA responses was observed. There was very poor agreement between TST and IGRA-PPD findings (k= 0.08) and between TST and IGRABCG findings (k= 0.02) Conclusion Analysis of TST and IGRA response to stimulation with BCG and PPD revealed no difference in immune response between BCG-vaccinated and non-vaccinated children; also no decrease of the BCG vaccine-induced cellular immune response over time was observed. We conclude that TST and IGRA have limitations in assessing a role of BCG or tuberculosis- related immunity. © 2015 Ranaivomanana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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