||Address:||The Jenner Institute, Old Road Campus Research Building
Roosevelt Drive, Oxford, OX3 7DQ
|Tel:||+44 (0)1865 617735|
|Principal areas of research:||T cells immunology, Malaria, Vaccines|
CD8+ T cells play a significant role in protection from liver-stage malaria, but due small number of infected liver cells and the short time that parasite are present in the liver, an exceptionally high numbers of circulating T cells are required to achieve protection. While traditional vaccination with heat-killed or attenuated vaccines has proved highly effective against pathogens controlled by neutralising antibodies, no vaccine has yet been licensed against pathogens in which cell mediated immunity plays an important role. Viral vaccines have shown a remarkable capacity to induce and boost T cells responses and antibodies and are therefore the primary focus for our development of vaccines against malaria, influenza and tuberculosis.
The primary focus of my research is to understand the immune response induced by vectored vaccines and in response to liver-stage malaria. I am particularly interested in the type of T cell response induced in terms of effector capacity (cytokines) and phenotype (effector/memory). I am interested in determining ways to increase the size of the immune response induced by vectored vaccines be that through altering vaccination regimens or through the co-expression of molecular adjuvants. This is complemented by work to identify new antigenic targets for a liver-stage malaria vaccine.
Spencer, A.J., et al. The Threshold of Protection from Liver-Stage Malaria Relies on a Fine Balance between the Number of Infected Hepatocytes and Effector CD8+ T Cells Present in the Liver. J Immunol, 198 (5), pp. 2006-2016 (2017)
Longley, R.J., et al. Assessment of the Plasmodium falciparum pre-erythrocytic antigen UIS3 as a potential candidate for a malaria vaccine. Infect Immun, 85 (3), pp. e00641-16-e00641-16 (2017)
Ewer KJ, Lambe T, Rollier CS, Spencer AJ, Hill AV, Dorrell L. Viral vectors as vaccine platforms: from immunogenicity to impact. Curr Opin Immunol. 2016 Jun 7;41:47-54.
Longley RJ, Hill AV, Spencer AJ. Malaria vaccines: identifying Plasmodium falciparum liver-stage targets. Front Microbiol. 2015 Sep 15;6:965
Longley RJ, Salman AM, Cottingham MG, Ewer K, Janse CJ, Khan SM, Spencer AJ, Hill AV. Comparative assessment of vaccine vectors encoding ten malaria antigens identifies two protective liver-stage candidates. Sci Rep. 2015 Jul 3;5:11820
Longley RJ, Bauza K, Ewer KJ, Hill AV, Spencer AJ. Development of an in vitro assay and demonstration of Plasmodium berghei liver-stage inhibition by TRAP-specific CD8+ T cells. PLoS One. 2015 Mar 30;10(3):e0119880
Spencer AJ, Furze J, Honeycutt JD, Colloca S, Ammendola V, Sridhar S, Calvert A, Saurya S, Wyllie DH, Gilbert SC, Bregu M, Cottingham MG, Hill AV. 4-1BBL enhances CD8+ T cell responses induced by vectored vaccines in mice but fails to improve immunogenicity in rhesus macaques. PLoS One. 2014 Aug 20;9(8):e105520
Spencer AJ, Bregu M, Rakasz E, Weisgrau KL, Jenks J, Longley RJ, Colloca S, Folgori A, Cortese R, Nicosia A, Cottingham MG, Hill AV. Enhanced Vaccine-Induced CD8+ T Cell Responses to Malaria Antigen ME-TRAP by Fusion to MHC Class II Invariant Chain. PLoS One. 2014 Jun 19;9(6):e100538
Sheehy SH, Spencer AJ, Douglas AD, Longley RJ, Edwards NJ, Williams AR, Poulton ID, Anagnostou NA, Roberts R, Kerridge S, Voysey M, James ER, Sim BKL, Billingsley PF, Lawrie AM, Hoffman SL, Hill AV. Optimising controlled human malaria infection studies using cryopreserved P. falciparum parasites administered by needle and syringe. PLoS One. 2013 Jun 18;8(6):e65960
Dicks MD, Spencer AJ, Edwards NJ, Wadell G, Bojang K, Gilbert SC, Hill AV, Cottingham MG. A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity. PLoS One. 2012;7(7):e40385
Lambe T, Spencer AJ, Mullarkey CE, Antrobus RD, Yu LM, de Whalley P, Thompson BA, Jones C, Chalk J, Kerridge S, Hill AV, Snape MD, Pollard AJ, Gilbert SC. T-cell responses in children to internal influenza antigens, 1 year after immunization with pandemic H1N1 influenza vaccine, and response to revaccination with seasonal trivalent-inactivated influenza vaccine. Pediatr Infect Dis J. 2012 Jun;31(6):e86-91