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Start Over Author "Hill, Adrian V S" Publisher american society for microbiology
39 results on '"Hill, Adrian V S"'

1. Preclinical Development and Assessment of Viral Vectors Expressing a Fusion Antigen of Plasmodium falciparum LSA1 and LSAP2 for Efficacy against Liver-Stage Malaria

Author

Halbroth, Benedict R., primary, Sebastian, Sarah, additional, Salman, Ahmed M., additional, Ulaszewska, Marta, additional, Gola, Anita, additional, Longley, Rhea J., additional, Janse, Chris J., additional, Khan, Shahid M., additional, Hill, Adrian V. S., additional, and Spencer, Alexandra J., additional

Published
2020
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2. Tailoring a Plasmodium vivax Vaccine To Enhance Efficacy through a Combination of a CSP Virus-Like Particle and TRAP Viral Vectors

Author

Atcheson, Erwan, Bauza, Karolis, Salman, Ahmed M., Alves, Eduardo, Blight, Joshua, Viveros-Sandoval, Martha Eva, Janse, Chris J., Khan, Shahid M., Hill, Adrian V. S., and Reyes-Sandoval, Arturo

Subjects
Squalene, Plasmodium berghei, Genetic Vectors, malaria, Protozoan Proteins, Antibodies, Protozoan, Polysorbates, Antigens, Protozoan, Vaccinia virus, Adenoviridae, Mice, Adjuvants, Immunologic, VLP, parasitic diseases, Malaria Vaccines, Malaria, Vivax, Animals, Vaccines, Virus-Like Particle, Mice, Inbred BALB C, vaccines, Saponins, adenoviruses, Microbial Immunity and Vaccines, Nanoparticles, Female, Plasmodium vivax
Abstract

Vivax malaria remains one of the most serious and neglected tropical diseases, with 132 to 391 million clinical cases per year and 2.5 billion people at risk of infection. A vaccine against Plasmodium vivax could have more impact than any other intervention, and the use of a vaccine targeting multiple antigens may result in higher efficacy against sporozoite infection than targeting a single antigen., Vivax malaria remains one of the most serious and neglected tropical diseases, with 132 to 391 million clinical cases per year and 2.5 billion people at risk of infection. A vaccine against Plasmodium vivax could have more impact than any other intervention, and the use of a vaccine targeting multiple antigens may result in higher efficacy against sporozoite infection than targeting a single antigen. Here, two leading P. vivax preerythrocytic vaccine candidate antigens, the P. vivax circumsporozoite protein (PvCSP) and the thrombospondin-related adhesion protein (PvTRAP) were delivered as a combined vaccine. This strategy provided a dose-sparing effect, with 100% sterile protection in mice using doses that individually conferred low or no protection, as with the unadjuvanted antigens PvTRAP (0%) and PvCSP (50%), and reached protection similar to that of adjuvanted components. Efficacy against malaria infection was assessed using a new mouse challenge model consisting of a double-transgenic Plasmodium berghei parasite simultaneously expressing PvCSP and PvTRAP used in mice immunized with the virus-like particle (VLP) Rv21 previously reported to induce high efficacy in mice using Matrix-M adjuvant, while PvTRAP was concomitantly administered in chimpanzee adenovirus and modified vaccinia virus Ankara (MVA) vectors (viral-vectored TRAP, or vvTRAP) to support effective induction of T cells. We examined immunity elicited by these vaccines in the context of two adjuvants approved for human use (AddaVax and Matrix-M). Matrix-M supported the highest anti-PvCSP antibody titers when combined with Rv21, and, interestingly, mixing PvCSP Rv21 and PvTRAP viral vectors enhanced immunity to malaria over levels provided by single vaccines.

Published
2018

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. 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. Efficacy of a Plasmodium vivax Malaria Vaccine Using ChAd63 and Modified Vaccinia Ankara Expressing Thrombospondin-Related Anonymous Protein as Assessed with Transgenic Plasmodium berghei Parasites

Author

Bauza, Karolis, Malinauskas, Tomas, Pfander, Claudia, Anar, Burcu, Jones, E Yvonne, Billker, Oliver, Hill, Adrian V S, Reyes-Sandoval, Arturo, Bauza, Karolis, Malinauskas, Tomas, Pfander, Claudia, Anar, Burcu, Jones, E Yvonne, Billker, Oliver, Hill, Adrian V S, and Reyes-Sandoval, Arturo

Abstract

Plasmodium vivax is the world's most widely distributed malaria parasite and a potential cause of morbidity and mortality for approximately 2.85 billion people living mainly in Southeast Asia and Latin America. Despite this dramatic burden, very few vaccines have been assessed in humans. The clinically relevant vectors modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAd63 are promising delivery systems for malaria vaccines due to their safety profiles and proven ability to induce protective immune responses against Plasmodium falciparum thrombospondin-related anonymous protein (TRAP) in clinical trials. Here, we describe the development of new recombinant ChAd63 and MVA vectors expressing P. vivax TRAP (PvTRAP) and show their ability to induce high antibody titers and T cell responses in mice. In addition, we report a novel way of assessing the efficacy of new candidate vaccines against P. vivax using a fully infectious transgenic Plasmodium berghei parasite expressing P. vivax TRAP to allow studies of vaccine efficacy and protective mechanisms in rodents. Using this model, we found that both CD8+ T cells and antibodies mediated protection against malaria using virus-vectored vaccines. Our data indicate that ChAd63 and MVA expressing PvTRAP are good preerythrocytic-stage vaccine candidates with potential for future clinical application.

Published
2014
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7. Correction for Nébié et al., Assessment of Chimpanzee Adenovirus Serotype 63 Neutralizing Antibodies Prior to Evaluation of a Candidate Malaria Vaccine Regimen Based on Viral Vectors

Author

Nébié, Issa, primary, Edwards, Nick J., additional, Tiono, Alfred B., additional, Ewer, Katie J., additional, Sanou, Guillaume S., additional, Soulama, Issiaka, additional, Sanon, Souleymane, additional, Diarra, Amidou, additional, Yaro, Jean Baptiste, additional, Kangoye, David, additional, Imoukhuede, Egeruan B., additional, Hill, Adrian V. S., additional, and Sirima, Sodiomon B., additional

Published
2014
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8. Assessment of Chimpanzee Adenovirus Serotype 63 Neutralizing Antibodies Prior to Evaluation of a Candidate Malaria Vaccine Regimen Based on Viral Vectors

Author

Nébié, Issa, primary, Edwards, Nick J., additional, Tiono, Alfred B., additional, Ewer, Katie J., additional, Sanou, Guillaume S., additional, Soulama, Issiaka, additional, Sanon, Souleymane, additional, Diarra, Amidou, additional, Yaro, Jean Baptiste, additional, Kangoye, David, additional, Imoukhuede, Egeruan B., additional, Hill, Adrian V. S., additional, and Sirima, Sodiomon B., additional

Published
2014
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10. Single Nucleotide Polymorphisms in the Toll-Like Receptor 3 and CD44 Genes Are Associated with Persistence of Vaccine-Induced Immunity to the Serogroup C Meningococcal Conjugate Vaccine

Author

Moore, Catrin E., primary, Hennig, Branwen J., additional, Perrett, Kirsten P., additional, Hoe, J. Claire, additional, Lee, Sue J., additional, Fletcher, Helen, additional, Brocklebank, Denise, additional, O'Connor, Daniel, additional, Snape, Matthew D., additional, Hall, Andrew J., additional, Segal, Shelley, additional, Hill, Adrian V. S., additional, and Pollard, Andrew J., additional

Published
2011
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12. Prime-Boost Immunization with Adenoviral and Modified Vaccinia Virus Ankara Vectors Enhances the Durability and Polyfunctionality of Protective Malaria CD8+T-Cell Responses

Author

Reyes-Sandoval, Arturo, primary, Berthoud, Tamara, additional, Alder, Nicola, additional, Siani, Loredana, additional, Gilbert, Sarah C., additional, Nicosia, Alfredo, additional, Colloca, Stefano, additional, Cortese, Riccardo, additional, and Hill, Adrian V. S., additional

Published
2011
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13. Immunogenicity and Protective Efficacy of Prime-Boost Regimens with Recombinant ΔureC hly+Mycobacterium bovis BCG and Modified Vaccinia Virus Ankara Expressing M. tuberculosis Antigen 85A against Murine Tuberculosis

Author

Tchilian, Elma Z., primary, Desel, Christiane, additional, Forbes, Emily K., additional, Bandermann, Silke, additional, Sander, Clare R., additional, Hill, Adrian V. S., additional, McShane, Helen, additional, and Kaufmann, Stefan H. E., additional

Published
2011
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16. Prime-Boost Immunization with Adenoviral and Modified Vaccinia Virus Ankara Vectors Enhances the Durability and Polyfunctionality of Protective Malaria CD8 + T-Cell Responses

Author

Reyes-Sandoval, Arturo, primary, Berthoud, Tamara, additional, Alder, Nicola, additional, Siani, Loredana, additional, Gilbert, Sarah C., additional, Nicosia, Alfredo, additional, Colloca, Stefano, additional, Cortese, Riccardo, additional, and Hill, Adrian V. S., additional

Published
2010
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18. Immunogenicity and Protective Efficacy of Prime-Boost Regimens with Recombinant Δ ureC hly + Mycobacterium bovis BCG and Modified Vaccinia Virus Ankara Expressing M. tuberculosis Antigen 85A against Murine Tuberculosis

Author

Tchilian, Elma Z., primary, Desel, Christiane, additional, Forbes, Emily K., additional, Bandermann, Silke, additional, Sander, Clare R., additional, Hill, Adrian V. S., additional, McShane, Helen, additional, and Kaufmann, Stefan H. E., additional

Published
2009
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20. Early Gamma Interferon and Interleukin-2 Responses to Vaccination Predict the Late Resting Memory in Malaria-Naïve and Malaria-Exposed Individuals

Author

Bejon, Philip, primary, Keating, Sheila, additional, Mwacharo, Jedidah, additional, Kai, Oscar K., additional, Dunachie, Susanna, additional, Walther, Michael, additional, Berthoud, Tamara, additional, Lang, Trudie, additional, Epstein, Judy, additional, Carucci, Daniel, additional, Moris, Philippe, additional, Cohen, Joe, additional, Gilbert, Sarah C., additional, Peshu, Norbert, additional, Marsh, Kevin, additional, and Hill, Adrian V. S., additional

Published
2006
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21. Safety, Immunogenicity, and Efficacy of Prime-Boost Immunization with Recombinant Poxvirus FP9 and Modified Vaccinia Virus Ankara Encoding the Full-Length Plasmodium falciparum Circumsporozoite Protein

Author

Walther, Michael, primary, Thompson, Fiona M., additional, Dunachie, Susanna, additional, Keating, Sheila, additional, Todryk, Stephen, additional, Berthoud, Tamara, additional, Andrews, Laura, additional, Andersen, Rikke F., additional, Moore, Anne, additional, Gilbert, Sarah C., additional, Poulton, Ian, additional, Dubovsky, Filip, additional, Tierney, Eveline, additional, Correa, Simon, additional, Huntcooke, Angela, additional, Butcher, Geoffrey, additional, Williams, Jack, additional, Sinden, Robert E., additional, and Hill, Adrian V. S., additional

Published
2006
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23. Invariant Vα14 Chain NKT Cells Promote Plasmodium berghei Circumsporozoite Protein-Specific Gamma Interferon- and Tumor Necrosis Factor Alpha-Producing CD8 + T Cells in the Liver after Poxvirus Vaccination of Mice

Author

Korten, Simone, primary, Anderson, Richard J., additional, Hannan, Carolyn M., additional, Sheu, Eric G., additional, Sinden, Robert, additional, Gadola, Stephan, additional, Taniguchi, Masaru, additional, and Hill, Adrian V. S., additional

Published
2005
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28. Induction of T Helper Type 1 and 2 Responses to 19-Kilodalton Merozoite Surface Protein 1 in Vaccinated Healthy Volunteers and Adults Naturally Exposed to Malaria

Author

Lee, Edwin A. M., primary, Palmer, Dupeh R., additional, Flanagan, Katie L., additional, Reece, William H. H., additional, Odhiambo, Kennedy, additional, Marsh, Kevin, additional, Pinder, Margaret, additional, Gravenor, Michael B., additional, Keitel, Wendy A., additional, Kester, Kent E., additional, Diggs, Carter, additional, Kaslow, David, additional, Apostolopoulos, V., additional, Ballou, W. Ripley, additional, Hill, Adrian V. S., additional, Krzych, Urszula, additional, and Plebanski, Magdalena, additional

Published
2002
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34. Single nucleotide polymorphisms in the Toll-like receptor 3 and CD44 genes are associated with persistence of vaccine-induced immunity to the serogroup C meningococcal conjugate vaccine.

Author

Moore CE, Hennig BJ, Perrett KP, Hoe JC, Lee SJ, Fletcher H, Brocklebank D, O'Connor D, Snape MD, Hall AJ, Segal S, Hill AV, and Pollard AJ

Subjects
Adolescent, Antibodies, Bacterial blood, Blood Bactericidal Activity, Child, Child, Preschool, Female, Genetic Association Studies, Humans, Immunoglobulin G blood, Infant, Male, Meningococcal Infections immunology, Time Factors, Young Adult, Hyaluronan Receptors genetics, Meningococcal Infections prevention & control, Meningococcal Vaccines immunology, Polymorphism, Single Nucleotide, Toll-Like Receptor 3 genetics
Abstract

The rate of decay of antibody concentration following serogroup C meningococcal (MenC) polysaccharide-protein conjugate vaccination varies between individuals. This depends partly on vaccination age but may be influenced by human genetics. We studied 721 single nucleotide polymorphisms (SNPs) across 131 candidate genes in a first cohort of 905 Caucasians (11 to 21 years old; mean time after vaccination, 4.9 years) and 30 SNPs across 17 genes in a replication study using 155 children, aged 6 to 12 years (mean time after vaccination, 6.7 years), and 196 infants (1 year old; mean time after vaccination, 8 months). Individuals were classified as responders or nonresponders for total MenC IgG concentration and MenC serum bactericidal antibody (SBA) measurements. Associated genes were examined further for quantitative outcome measures. Fifty-nine SNPs in 37 genes were associated with IgG persistence (adjusted for age at measurement), and 56 SNPs in 36 genes were associated with SBA persistence (adjusted for age at measurement and vaccine used). Three SNPs each within the Toll-like receptor 3 (TLR3) (rs3775291, rs3775292, and rs5743312) and CD44 (rs11033013, rs353644, and rs996076) genes were associated with IgG (adjusted for age at measurement) or SBA (adjusted for age at measurement and vaccine used) persistence in the initial genetic study (P, 0.02 to 0.04). Single SNPs within the TLR3 (rs7657186) (P = 0.004 [unadjusted]) and CD44 (rs12419062) (P = 0.01 [unadjusted]) genes were associated with IgG persistence in the replication study. These results suggest that genetic polymorphisms in the TLR3 and CD44 genes are associated with the persistence of the immune response to MenC vaccines 1 to 6 years after vaccination.

Published
2012
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35. Prime-boost immunization with adenoviral and modified vaccinia virus Ankara vectors enhances the durability and polyfunctionality of protective malaria CD8+ T-cell responses.

Author

Reyes-Sandoval A, Berthoud T, Alder N, Siani L, Gilbert SC, Nicosia A, Colloca S, Cortese R, and Hill AV

Subjects
Adenoviridae, Animals, CD8-Positive T-Lymphocytes immunology, Female, Immunization Schedule, Mice, Mice, Inbred BALB C, Protozoan Proteins immunology, Vaccines, Synthetic administration & dosage, Vaccines, Synthetic immunology, Vaccinia virus classification, CD8-Positive T-Lymphocytes physiology, Immunization, Secondary, Malaria Vaccines administration & dosage, Malaria Vaccines immunology, Malaria, Falciparum prevention & control
Abstract

Protection against liver-stage malaria relies on the induction of high frequencies of antigen-specific CD8+ T cells. We have previously reported high protective levels against mouse malaria, albeit short-lived, by a single vaccination with adenoviral vectors coding for a liver-stage antigen (ME.TRAP). Here, we report that prime-boost regimens using modified vaccinia virus Ankara (MVA) and adenoviral vectors encoding ME.TRAP can enhance both short- and long-term sterile protection against malaria. Protection persisted for at least 6 months when simian adenoviruses AdCh63 and AdC9 were used as priming vectors. Kinetic analysis showed that the MVA boost made the adenoviral-primed T cells markedly more polyfunctional, with the number of gamma interferon (INF-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-2 (IL-2) triple-positive and INF-gamma and TNF-alpha double-positive cells increasing over time, while INF-gamma single-positive cells declined with time. However, IFN-gamma production prevailed as the main immune correlate of protection, while neither an increase of polyfunctionality nor a high integrated mean fluorescence intensity (iMFI) correlated with protection. These data highlight the ability of optimized viral vector prime-boost regimens to generate more protective and sustained CD8+ T-cell responses, and our results encourage a more nuanced assessment of the importance of inducing polyfunctional CD8(+) T cells by vaccination.

Published
2010
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36. Immunogenicity and protective efficacy of prime-boost regimens with recombinant (delta)ureC hly+ Mycobacterium bovis BCG and modified vaccinia virus ankara expressing M. tuberculosis antigen 85A against murine tuberculosis.

Author

Tchilian EZ, Desel C, Forbes EK, Bandermann S, Sander CR, Hill AV, McShane H, and Kaufmann SH

Subjects
Acyltransferases genetics, Animals, Antigens, Bacterial genetics, CD8-Positive T-Lymphocytes immunology, Female, Gene Expression Regulation, Bacterial, Genetic Engineering, Immunization, Secondary, Mice, Mice, Inbred BALB C, Mycobacterium bovis metabolism, Recombinant Proteins, Tuberculin Test, Acyltransferases metabolism, Antigens, Bacterial metabolism, BCG Vaccine immunology, Mycobacterium bovis genetics, Tuberculosis, Pulmonary immunology, Vaccinia virus genetics
Abstract

In the light of the recent emergence of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, the epidemic of tuberculosis (TB) in populations coinfected with human immunodeficiency virus, and the failure of Mycobacterium bovis bacillus Calmette-Guerin (BCG) to protect against disease, new vaccines against TB are urgently needed. Two promising new vaccine candidates are the recombinant DeltaureC hly(+) BCG (recBCG), which has been developed to replace the current BCG vaccine strain, and modified vaccinia virus Ankara (MVA) expressing M. tuberculosis antigen 85A (MVA85A), which is a leading candidate vaccine designed to boost the protective efficacy of BCG. In the present study, we examined the effect of MVA85A boosting on the protection afforded at 12 weeks postchallenge by BCG and recBCG by using bacterial CFU as an efficacy readout. recBCG-immunized mice were significantly better protected against aerosol challenge with M. tuberculosis than mice immunized with the parental strain of BCG. Intradermal boosting with MVA85A did not reduce the bacterial burden any further. In order to identify a marker for the development of a protective immune response against M. tuberculosis challenge, we analyzed splenocytes after priming or prime-boosting by using intracytoplasmic cytokine staining and assays for cytokine secretion. Boosting with MVA85A, but not priming with BCG or recBCG, greatly increased the antigen 85A-specific T-cell response, suggesting that the mechanism of protection may differ from that against BCG or recBCG. We show that the numbers of systemic multifunctional cytokine-producing cells did not correlate with protection against aerosol challenge in BALB/c mice. This emphasizes the need for new biomarkers for the evaluation of TB vaccine efficacy.

Published
2009
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37. Invariant Valpha14 chain NKT cells promote Plasmodium berghei circumsporozoite protein-specific gamma interferon- and tumor necrosis factor alpha-producing CD8+ T cells in the liver after poxvirus vaccination of mice.

Author

Korten S, Anderson RJ, Hannan CM, Sheu EG, Sinden R, Gadola S, Taniguchi M, and Hill AV

Subjects
Animals, CD8-Positive T-Lymphocytes metabolism, Interferon-gamma metabolism, Killer Cells, Natural immunology, Kinetics, Liver immunology, Malaria immunology, Mice, Plasmodium berghei immunology, Poxviridae Infections immunology, Poxviridae Infections prevention & control, Spleen immunology, Spleen metabolism, T-Lymphocyte Subsets immunology, Tumor Necrosis Factor-alpha metabolism, Antigens, Differentiation, B-Lymphocyte immunology, CD8-Positive T-Lymphocytes immunology, Histocompatibility Antigens Class II immunology, Malaria metabolism, Plasmodium berghei metabolism, Poxviridae immunology, Vaccines immunology
Abstract

Understanding the protective mechanism in the liver induced by recombinant vaccines against the pre-erythrocytic stages of malaria is important for vaccine development. Most studies in mice have focused on splenic and peripheral blood T cells and identified gamma interferon (IFN-gamma)-producing CD8+ T cells as correlates of protection, which can be induced by prime-boost vaccination with recombinant poxviruses. Invariant natural killer T (Valpha14iNKT) cells can also protect against liver stage malaria, when activated, and are abundant in the liver. Since poxviruses have nonspecific immunomodulating effects, which are incompletely understood, we investigated whether recombinant poxviruses affect the protective properties of hepatic Valpha14iNKT cells and thus vaccine efficacy. We show that intradermal vaccination with recombinant poxviruses activated Valpha14iNKT cells and NK cells in the livers of BALB/c mice while inducing IFN-gamma- and tumor necrosis factor alpha (TNF-alpha)-producing pre-erythrocytic stage antigen-specific CD8+ T cells. Greater numbers of hepatic Valpha14iNKT cells secreted interleukin-4 than IFN-gamma. Vaccinated Valpha14iNKT-cell-deficient mice had lower, but still protective levels of hepatic and splenic IFN-gamma+ and TNF-alpha+ CD8+ T cells and better protection rates later after challenge with Plasmodium berghei sporozoites. Therefore, vaccine-activated hepatic Valpha14iNKT cells help in generating specific T cells but are not required for protection induced by recombinant poxviruses. Furthermore, double-positive INF-gamma+/TNF-alpha+ CD8+ T cells were enriched in protected livers, suggesting that cells expressing both of these cytokines may be most relevant for protection.

Published
2005
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38. Lack of association between Toll-like receptor 2 polymorphisms and susceptibility to severe disease caused by Staphylococcus aureus.

Author

Moore CE, Segal S, Berendt AR, Hill AV, and Day NP

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Toll-Like Receptor 2, Toll-Like Receptors, Genetic Predisposition to Disease, Membrane Glycoproteins genetics, Polymorphism, Single Nucleotide genetics, Receptors, Cell Surface genetics, Staphylococcal Infections genetics, Staphylococcus aureus
Abstract

To investigate a putative link between genetically determined variations in Toll-like receptor 2 (TLR2) and the occurrence of severe Staphylococcus aureus infection, the functional Arg753Gln single-nucleotide polymorphism and the GT repeat microsatellite in the TLR2 gene were examined in a large case-control study. No associations with disease or mortality attributable to these features were found.

Published
2004
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39. Protective immunity against Mycobacterium tuberculosis induced by dendritic cells pulsed with both CD8(+)- and CD4(+)-T-cell epitopes from antigen 85A.

Author

McShane H, Behboudi S, Goonetilleke N, Brookes R, and Hill AV

Subjects
Amino Acid Sequence, Animals, Antigen Presentation, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Epitopes, Female, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Acyltransferases, Antigens, Bacterial therapeutic use, BCG Vaccine therapeutic use, Dendritic Cells transplantation, Tuberculosis prevention & control, Vaccination
Abstract

Immunization with DNA followed by modified vaccinia virus Ankara strain, both expressing the antigen 85A, induced both CD4(+)- and CD8(+)-T-cell responses in BALB/c mice. Following challenge with Mycobacterium tuberculosis, this prime-boost regimen produced protection equivalent to that conferred by Mycobacterium bovis BCG. Following immunization with dendritic cells pulsed with an antigen 85A CD4(+)- or CD8(+)-restricted epitope, alone or in combination, copresentation of both epitopes on the same dendritic cell was required for protection, demonstrating that induced CD8(+) T cells can play a protective role against tuberculosis.

Published
2002
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