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9 results on '"Lall, Amar"'

3. Evaluation of Plasmodium vivax Cell-Traversal Protein for Ookinetes and Sporozoites as a Preerythrocytic P. vivax Vaccine

Author

Alves, Eduardo, Salman, Ahmed M, De Souza Leoratti, Fabiana Maria, Lopez-Camacho, Cesar, Viveros-Sandoval, Martha Eva, Lall, Amar, El-Turabi, Aadil, Bachmann, Martin, Hill, Adrian V S, Janse, Chris J, Khan, Shahid M, and Reyes-Sandoval, Arturo

Subjects
610 Medicine & health, complex mixtures
Abstract

Four different vaccine platforms, each targeting the human malaria parasite Plasmodium vivax cell-traversal protein for ookinetes and sporozoites (PvCelTOS), were generated and assessed for protective efficacy. These platforms consisted of a recombinant chimpanzee adenoviral vector 63 (ChAd63) expressing PvCelTOS (Ad), a recombinant modified vaccinia virus Ankara expressing PvCelTOS (MVA), PvCelTOS conjugated to bacteriophage Qβ virus-like particles (VLPs), and a recombinant PvCelTOS protein expressed in eukaryotic HEK293T cells (protein). Inbred BALB/c mice and outbred CD-1 mice were immunized using the following prime-boost regimens: Ad-MVA, Ad-VLPs, and Ad-protein. Protective efficacy against sporozoite challenge was assessed after immunization using a novel chimeric rodent Plasmodium berghei parasite (Pb-PvCelTOS). This chimeric parasite expresses P. vivax CelTOS in place of the endogenous P. berghei CelTOS and produces fully infectious sporozoites. A single Ad immunization in BALB/c and CD-1 mice induced anti-PvCelTOS antibodies which were boosted efficiently using MVA, VLP, or protein immunization. PvCelTOS-specific gamma interferon- and tumor necrosis factor alpha-producing CD8+ T cells were induced at high frequencies by all prime-boost regimens in BALB/c mice but not in CD-1 mice; in CD-1 mice, they were only marginally increased after boosting with MVA. Despite the induction of anti-PvCelTOS antibodies and PvCelTOS-specific CD8+ T-cell responses, only low levels of protective efficacy against challenge with Pb-PvCelTOS sporozoites were obtained using any immunization strategy. In BALB/c mice, no immunization regimens provided significant protection against a Pb-PvCelTOS chimeric sporozoite challenge. In CD-1 mice, modest protective efficacy against challenge with chimeric P. berghei sporozoites expressing either PvCelTOS or P. falciparum CelTOS was observed using the Ad-protein vaccination regimen.

Published
2017
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4. Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models

Author

Salman, Ahmed M., primary, Montoya-Díaz, Eduardo, additional, West, Heather, additional, Lall, Amar, additional, Atcheson, Erwan, additional, Lopez-Camacho, Cesar, additional, Ramesar, Jai, additional, Bauza, Karolis, additional, Collins, Katharine A., additional, Brod, Florian, additional, Reis, Fernando, additional, Pappas, Leontios, additional, González-Cerón, Lilia, additional, Janse, Chris J., additional, Hill, Adrian V. S., additional, Khan, Shahid M., additional, and Reyes-Sandoval, Arturo, additional

Published
2017
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5. Evaluation of Plasmodium vivax Cell-Traversal Protein for Ookinetes and Sporozoites as a Preerythrocytic P. vivax Vaccine

Author

Alves, Eduardo, primary, Salman, Ahmed M., additional, Leoratti, Fabiana, additional, Lopez-Camacho, Cesar, additional, Viveros-Sandoval, Martha Eva, additional, Lall, Amar, additional, El-Turabi, Aadil, additional, Bachmann, Martin F., additional, Hill, Adrian V. S., additional, Janse, Chris J., additional, Khan, Shahid M., additional, and Reyes-Sandoval, Arturo, additional

Published
2017
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6. Defining the range of pathogens susceptible to Ifitm3 restriction using a knockout mouse model

Author

Everitt, Aaron R, Clare, Simon, McDonald, Jacqueline U, Kane, Leanne, Harcourt, Katherine, Ahras, Malika, Lall, Amar, Hale, Christine, Rodgers, Angela, Young, Douglas B, Haque, Ashraful, Billker, Oliver, Tregoning, John S, Dougan, Gordon, Kellam, Paul, Everitt, Aaron R, Clare, Simon, McDonald, Jacqueline U, Kane, Leanne, Harcourt, Katherine, Ahras, Malika, Lall, Amar, Hale, Christine, Rodgers, Angela, Young, Douglas B, Haque, Ashraful, Billker, Oliver, Tregoning, John S, Dougan, Gordon, and Kellam, Paul

Abstract

The interferon-inducible transmembrane (IFITM) family of proteins has been shown to restrict a broad range of viruses in vitro and in vivo by halting progress through the late endosomal pathway. Further, single nucleotide polymorphisms (SNPs) in its sequence have been linked with risk of developing severe influenza virus infections in humans. The number of viruses restricted by this host protein has continued to grow since it was first demonstrated as playing an antiviral role; all of which enter cells via the endosomal pathway. We therefore sought to test the limits of antimicrobial restriction by Ifitm3 using a knockout mouse model. We showed that Ifitm3 does not impact on the restriction or pathogenesis of bacterial (Salmonella typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis) or protozoan (Plasmodium berghei) pathogens, despite in vitro evidence. However, Ifitm3 is capable of restricting respiratory syncytial virus (RSV) in vivo either through directly restricting RSV cell infection, or by exerting a previously uncharacterised function controlling disease pathogenesis. This represents the first demonstration of a virus that enters directly through the plasma membrane, without the need for the endosomal pathway, being restricted by the IFITM family; therefore further defining the role of these antiviral proteins.

Published
2013
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7. Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley Fever vaccine in mice

Author

Warimwe, George M, primary, Lorenzo, Gema, additional, Lopez-Gil, Elena, additional, Reyes-Sandoval, Arturo, additional, Cottingham, Matthew G, additional, Spencer, Alexandra J, additional, Collins, Katharine A, additional, Dicks, Matthew DJ, additional, Milicic, Anita, additional, Lall, Amar, additional, Furze, Julie, additional, Turner, Alison V, additional, Hill, Adrian VS, additional, Brun, Alejandro, additional, and Gilbert, Sarah C, additional

Published
2013
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8. Defining the Range of Pathogens Susceptible to Ifitm3 Restriction Using a Knockout Mouse Model

Author

Everitt, Aaron R., primary, Clare, Simon, additional, McDonald, Jacqueline U., additional, Kane, Leanne, additional, Harcourt, Katherine, additional, Ahras, Malika, additional, Lall, Amar, additional, Hale, Christine, additional, Rodgers, Angela, additional, Young, Douglas B., additional, Haque, Ashraful, additional, Billker, Oliver, additional, Tregoning, John S., additional, Dougan, Gordon, additional, and Kellam, Paul, additional

Published
2013
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9. Evaluation of Plasmodium vivaxCell-Traversal Protein for Ookinetes and Sporozoites as a Preerythrocytic P. vivaxVaccine

Author

Alves, Eduardo, Salman, Ahmed M., Leoratti, Fabiana, Lopez-Camacho, Cesar, Viveros-Sandoval, Martha Eva, Lall, Amar, El-Turabi, Aadil, Bachmann, Martin F., Hill, Adrian V. S., Janse, Chris J., Khan, Shahid M., and Reyes-Sandoval, Arturo

Abstract

ABSTRACTFour different vaccine platforms, each targeting the human malaria parasite Plasmodium vivaxcell-traversal protein for ookinetes and sporozoites (PvCelTOS), were generated and assessed for protective efficacy. These platforms consisted of a recombinant chimpanzee adenoviral vector 63 (ChAd63) expressing PvCelTOS (Ad), a recombinant modified vaccinia virus Ankara expressing PvCelTOS (MVA), PvCelTOS conjugated to bacteriophage Qß virus-like particles (VLPs), and a recombinant PvCelTOS protein expressed in eukaryotic HEK293T cells (protein). Inbred BALB/c mice and outbred CD-1 mice were immunized using the following prime-boost regimens: Ad-MVA, Ad-VLPs, and Ad-protein. Protective efficacy against sporozoite challenge was assessed after immunization using a novel chimeric rodent Plasmodium bergheiparasite (Pb-PvCelTOS). This chimeric parasite expresses P. vivaxCelTOS in place of the endogenous P. bergheiCelTOS and produces fully infectious sporozoites. A single Ad immunization in BALB/c and CD-1 mice induced anti-PvCelTOS antibodies which were boosted efficiently using MVA, VLP, or protein immunization. PvCelTOS-specific gamma interferon- and tumor necrosis factor alpha-producing CD8+T cells were induced at high frequencies by all prime-boost regimens in BALB/c mice but not in CD-1 mice; in CD-1 mice, they were only marginally increased after boosting with MVA. Despite the induction of anti-PvCelTOS antibodies and PvCelTOS-specific CD8+T-cell responses, only low levels of protective efficacy against challenge with Pb-PvCelTOS sporozoites were obtained using any immunization strategy. In BALB/c mice, no immunization regimens provided significant protection against a Pb-PvCelTOS chimeric sporozoite challenge. In CD-1 mice, modest protective efficacy against challenge with chimeric P. bergheisporozoites expressing either PvCelTOS or P. falciparumCelTOS was observed using the Ad-protein vaccination regimen.

Published
2017
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