Infect. Immun., Dec 1997, 5082-5087, Vol 65, No. 12
Copyright © 1997, American Society for Microbiology

T-cell immunity to peptide epitopes of liver-stage antigen 1 in an area of Papua New Guinea in which malaria is holoendemic

M Connelly, CL King, K Bucci, S Walters, B Genton, MP Alpers, M Hollingdale and JW Kazura
Division of Geographic Medicine, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4983, USA.

Liver-stage antigen 1 (LSA1) is one of several pre-erythrocytic antigens considered for inclusion in a multiantigen, multistage subunit vaccine against falciparum malaria. We examined T-cell proliferation and cytokine responses to peptides corresponding to amino acids 84 to 107, 1813 to 1835, and 1888 to 1909 of LSA1 in asymptomatic adults living in an area of Papua New Guinea where malaria is holoendemic. Whereas T cells from North Americans never exposed to malaria did not respond to any of the peptides, those from 52 of 55 adults from the area where malaria is endemic had vigorous proliferation responses to one or more of the LSA1 peptides (mean stimulation indices of 6.8 to 7.2). Gamma interferon (IFN-gamma) production driven by LSA1 peptides ranged from 34 to more than 3,500 pg/2 x 10(6) cells, was derived primarily from CD8+ cells, and was dissociated from T-cell proliferation. The frequencies of IFN-gamma response to the amino acid 1819 to 1835 and 1888 to 1909 peptides were significantly greater than that to the amino acid 84 to 107 peptide (87 and 88% versus 33% of subjects; P < 0.0001). In contrast to proliferation and IFN-gamma, interleukin 4 (IL-4) and/or IL-5 responses to LSA1 peptides were detected in only 18% of the subjects. These data show that T-cell immunity to epitopes in the N- and C-terminal regions of LSA1 are common in persons living in this area of Papua New Guinea where malaria is endemic. The dominance of type 1 CD8 cell IFN-gamma responses is consistent with a role for this T-cell population in immunity to liver- stage Plasmodium falciparum in humans.

This article has been cited by other articles:

• Siddiqui, A. A., Bora, H., Singh, N., Dash, A. P., Sharma, Y. D. (2008). Expression, Purification, and Characterization of the Immunological Response to a 40-Kilodalton Plasmodium vivax Tryptophan-Rich Antigen. Infect. Immun. 76: 2576-2586 [Abstract] [Full Text]  
• Rodriguez, A., Goudsmit, J., Companjen, A., Mintardjo, R., Gillissen, G., Tax, D., Sijtsma, J., Weverling, G. J., Holterman, L., Lanar, D. E., Havenga, M. J. E., Radosevic, K. (2008). Impact of Recombinant Adenovirus Serotype 35 Priming versus Boosting of a Plasmodium falciparum Protein: Characterization of T- and B-Cell Responses to Liver-Stage Antigen 1. Infect. Immun. 76: 1709-1718 [Abstract] [Full Text]  
• Pichyangkul, S., Kum-Arb, U., Yongvanitchit, K., Limsalakpetch, A., Gettayacamin, M., Lanar, D. E., Ware, L. A., Stewart, V. A., Heppner, D. G., Mettens, P., Cohen, J. D., Ballou, W. R., Fukuda, M. M. (2008). Preclinical Evaluation of the Safety and Immunogenicity of a Vaccine Consisting of Plasmodium falciparum Liver-Stage Antigen 1 with Adjuvant AS01B Administered Alone or Concurrently with the RTS,S/AS01B Vaccine in Rhesus Primates. Infect. Immun. 76: 229-238 [Abstract] [Full Text]  
• Brando, C., Ware, L. A., Freyberger, H., Kathcart, A., Barbosa, A., Cayphas, S., Demoitie, M.-A., Mettens, P., Heppner, D. G., Lanar, D. E. (2007). Murine Immune Responses to Liver-Stage Antigen 1 Protein FMP011, a Malaria Vaccine Candidate, Delivered with Adjuvant AS01B or AS02A. Infect. Immun. 75: 838-845 [Abstract] [Full Text]  
• JOHN, C. C., MOORMANN, A. M., PREGIBON, D. C., SUMBA, P. O., MCHUGH, M. M., NARUM, D. L., LANAR, D. E., SCHLUCHTER, M. D., KAZURA, J. W. (2005). CORRELATION OF HIGH LEVELS OF ANTIBODIES TO MULTIPLE PRE-ERYTHROCYTIC PLASMODIUM FALCIPARUM ANTIGENS AND PROTECTION FROM INFECTION. Am J Trop Med Hyg 73: 222-228 [Abstract] [Full Text]  
• Hillier, C. J., Ware, L. A., Barbosa, A., Angov, E., Lyon, J. A., Heppner, D. G., Lanar, D. E. (2005). Process Development and Analysis of Liver-Stage Antigen 1, a Preerythrocyte-Stage Protein-Based Vaccine for Plasmodium falciparum. Infect. Immun. 73: 2109-2115 [Abstract] [Full Text]  
• John, C. C., Moormann, A. M., Sumba, P. O., Ofulla, A. V., Pregibon, D. C., Kazura, J. W. (2004). Gamma Interferon Responses to Plasmodium falciparum Liver-Stage Antigen 1 and Thrombospondin-Related Adhesive Protein and Their Relationship to Age, Transmission Intensity, and Protection against Malaria. Infect. Immun. 72: 5135-5142 [Abstract] [Full Text]  
• Berenzon, D., Schwenk, R. J., Letellier, L., Guebre-Xabier, M., Williams, J., Krzych, U. (2003). Protracted Protection to Plasmodium berghei Malaria Is Linked to Functionally and Phenotypically Heterogeneous Liver Memory CD8+ T Cells. J. Immunol. 171: 2024-2034 [Abstract] [Full Text]  
• John, C. C., Zickafoose, J. S., Sumba, P. O., King, C. L., Kazura, J. W. (2003). Antibodies to the Plasmodium falciparum Antigens Circumsporozoite Protein, Thrombospondin-Related Adhesive Protein, and Liver-Stage Antigen 1 Vary by Ages of Subjects and by Season in a Highland Area of Kenya. Infect. Immun. 71: 4320-4325 [Abstract] [Full Text]  
• ONG'ECHA, J. M. O., LAL, A. A., TERLOUW, D. J., TER KUILE, F. O., KARIUKI, S. K., UDHAYAKUMAR, V., ORAGO, A. S. S., HIGHTOWER, A. W., NAHLEN, B. L., SHI, Y. P. (2003). ASSOCIATION OF INTERFERON-{gamma} RESPONSES TO PRE-ERYTHROCYTIC STAGE VACCINE CANDIDATE ANTIGENS OF PLASMODIUM FALCIPARUM IN YOUNG KENYAN CHILDREN WITH IMPROVED HEMOGLOBIN LEVELS: XV. ASEMBO BAY COHORT PROJECT. Am J Trop Med Hyg 68: 590-597 [Abstract] [Full Text]  
• Joshi, M. B., Gam, A. A., Boykins, R. A., Kumar, S., Sacci, J., Hoffman, S. L., Nakhasi, H. L., Kenney, R. T. (2001). Immunogenicity of Well-Characterized Synthetic Plasmodium falciparum Multiple Antigen Peptide Conjugates. Infect. Immun. 69: 4884-4890 [Abstract] [Full Text]  
• John, C. C., Sumba, P. O., Ouma, J. H., Nahlen, B. L., King, C. L., Kazura, J. W. (2000). Cytokine Responses to Plasmodium falciparum Liver-Stage Antigen 1 Vary in Rainy and Dry Seasons in Highland Kenya. Infect. Immun. 68: 5198-5204 [Abstract] [Full Text]  
• Doolan, D. L., Southwood, S., Chesnut, R., Appella, E., Gomez, E., Richards, A., Higashimoto, Y. I., Maewal, A., Sidney, J., Gramzinski, R. A., Mason, C., Koech, D., Hoffman, S. L., Sette, A. (2000). HLA-DR-Promiscuous T Cell Epitopes from Plasmodium falciparum Pre-Erythrocytic-Stage Antigens Restricted by Multiple HLA Class II Alleles. J. Immunol. 165: 1123-1137 [Abstract] [Full Text]  
• Joshi, S. K., Bharadwaj, A., Chatterjee, S., Chauhan, V. S. (2000). Analysis of Immune Responses against T- and B-Cell Epitopes from Plasmodium falciparum Liver-Stage Antigen 1 in Rodent Malaria Models and Malaria-Exposed Human Subjects in India. Infect. Immun. 68: 141-150 [Abstract] [Full Text]  
• Kurtis, J. D., Lanar, D. E., Opollo, M., Duffy, P. E. (1999). Interleukin-10 Responses to Liver-Stage Antigen 1 Predict Human Resistance to Plasmodium falciparum. Infect. Immun. 67: 3424-3429 [Abstract] [Full Text]