Browsing by Author "Anjali Yadava"

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    Asymptomatic Plasmodium vivax infections induce robust IgG responses to multiple blood-stage proteins in a low-transmission region of western Thailand
    (2017-04-28) Rhea J. Longley; Camila T. França; Michael T. White; Chalermpon Kumpitak; Patiwat Sa-Angchai; Jakub Gruszczyk; Jessica B. Hostetler; Anjali Yadava; Christopher L. King; Rick M. Fairhurst; Julian C. Rayner; Wai Hong Tham; Wang Nguitragool; Jetsumon Sattabongkot; Ivo Mueller; Walter and Eliza Hall Institute of Medical Research; Mahidol University; University of Melbourne; Imperial College London; Wellcome Trust Sanger Institute; National Institute of Allergy and Infectious Diseases; Walter Reed Army Institute of Research; Case Western Reserve University; Instituto de Salud Global de Barcelona; Institut Pasteur, Paris
    © 2017 The Author(s). Background: Thailand is aiming to eliminate malaria by the year 2024. Plasmodium vivax has now become the dominant species causing malaria within the country, and a high proportion of infections are asymptomatic. A better understanding of antibody dynamics to P. vivax antigens in a low-transmission setting, where acquired immune responses are poorly characterized, will be pivotal for developing new strategies for elimination, such as improved surveillance methods and vaccines. The objective of this study was to characterize total IgG antibody levels to 11 key P. vivax proteins in a village of western Thailand. Methods: Plasma samples from 546 volunteers enrolled in a cross-sectional survey conducted in 2012 in Kanchanaburi Province were utilized. Total IgG levels to 11 different proteins known or predicted to be involved in reticulocyte binding or invasion (ARP, GAMA, P41, P12, PVX_081550, and five members of the PvRBP family), as well as the leading pre-erythrocytic vaccine candidate (CSP) were measured using a multiplexed bead-based assay. Associations between IgG levels and infection status, age, and spatial location were explored. Results: Individuals from a low-transmission region of western Thailand reacted to all 11 P. vivax recombinant proteins. Significantly greater IgG levels were observed in the presence of a current P. vivax infection, despite all infected individuals being asymptomatic. IgG levels were also higher in adults (18 years and older) than in children. For most of the proteins, higher IgG levels were observed in individuals living closer to the Myanmar border and further away from local health services. Conclusions: Robust IgG responses were observed to most proteins and IgG levels correlated with surrogates of exposure, suggesting these antigens may serve as potential biomarkers of exposure, immunity, or both.
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    Evaluation of immune responses to a Plasmodium vivax CSP-based recombinant protein vaccine candidate in combination with second-generation adjuvants in mice
    (2012-05-09) Joanne M. Lumsden; Saule Nurmukhambetova; Jennifer H. Klein; Jetsumon Sattabongkot; Jason W. Bennett; Sylvie Bertholet; Christopher B. Fox; Steven G. Reed; Christian F. Ockenhouse; Randall F. Howard; Mark E. Polhemus; Anjali Yadava; Walter Reed Army Institute of Research; Armed Forces Medical Research Institute of Science; Infectious Disease Research Institute; Mahidol University
    Plasmodium vivax is the major cause of malaria outside of sub-Saharan Africa and causes morbidity and results in significant economic impact in developing countries. In order to produce a P. vivax vaccine for global use, we have previously reported the development of VMP001, based on the circumsporozoite protein (CSP) of P. vivax. Our interest is to evaluate second-generation vaccine formulations to identify novel combinations of adjuvants capable of inducing strong, long-lasting immune responses. In this study, groups of C57BL/6J mice were immunized subcutaneously three times with VMP001 emulsified with synthetic TLR4 (GLA) or TLR7/8 (R848) agonist in stable emulsion (SE), a combination of the TLR4 and TLR7/8 agonists, or SE alone. Sera and splenocytes were tested for the presence of antigen-specific humoral and cellular responses, respectively. All groups of mice generated high titers of anti-P. vivax IgG antibodies as detected by ELISA and immunofluorescence assay. GLA-SE promoted a shift in the antibody response to a Th1 profile, as demonstrated by the change in IgG2c/IgG1 ratio. In addition, GLA-SE induced a strong cellular immune response characterized by multi-functional, antigen-specific CD4 + T cells secreting IL-2, TNF and IFN-γ. In contrast, mice immunized with SE or R848-SE produced low numbers of antigen-specific CD4 + T cells, and these T cells secreted IL-2 and TNF, but not IFN-γ. Finally, R848-SE did not enhance the immune response compared to GLA-SE alone. Based on these results, we conclude that the combination of VMP001 and GLA-SE is highly immunogenic in mice and may serve as a potential second-generation vaccine candidate against vivax malaria. © 2012.