Abstract
A blood-stage malaria antigen comprising the C terminus of merozoite surface protein 1 fused to glutathione S-transferase, combined with an adjuvant formulation containing squalane, Tween 80, and pluronic L121 (AF), administered subcutaneously protected mice against death from a lethal Plasmodium yoelii infection. The protection induced by this antigen-adjuvant combination was compared with that induced by the antigen plus saponin in terms of survival from the lethal infection and clearance of parasitemia. The levels of gamma interferon and interleukin-4 in spleens were measured as indicators of Th1 and Th2 cell activation, and antibody classes and subclasses were determined by immunofluorescence. With a 10-micrograms dose of antigen and AF as adjuvant, all mice recovered, but with saponin as the adjuvant, there were only a few survivors. With 30 micrograms of antigen plus AF, the peak parasitemias were 10-fold lower than those with 10 micrograms; with saponin, survival was slightly improved. The levels of both gamma interferon and interleukin-4 rose more rapidly and to higher levels with AF as the adjuvant than with saponin, and the same was true for immunoglobulin G1 (IgG1), IgG2a, and IgG2b subclasses. Thus, in terms of both cytokine production and antibody levels, AF is a more potent adjuvant for a malaria vaccine than is saponin.
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- Calvo P. A., Daly T. M., Long C. A. Plasmodium yoelii: the role of the individual epidermal growth factor-like domains of the merozoite surface protein-1 in protection from malaria. Exp Parasitol. 1996 Jan;82(1):54–64. doi: 10.1006/expr.1996.0007. [DOI] [PubMed] [Google Scholar]
- Daly T. M., Long C. A. A recombinant 15-kilodalton carboxyl-terminal fragment of Plasmodium yoelii yoelii 17XL merozoite surface protein 1 induces a protective immune response in mice. Infect Immun. 1993 Jun;61(6):2462–2467. doi: 10.1128/iai.61.6.2462-2467.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finkelman F. D., Katona I. M., Mosmann T. R., Coffman R. L. IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol. 1988 Feb 15;140(4):1022–1027. [PubMed] [Google Scholar]
- Freeman R. R., Holder A. A. Characteristics of the protective response of BALB/c mice immunized with a purified Plasmodium yoelii schizont antigen. Clin Exp Immunol. 1983 Dec;54(3):609–616. [PMC free article] [PubMed] [Google Scholar]
- Herrera M. A., Rosero F., Herrera S., Caspers P., Rotmann D., Sinigaglia F., Certa U. Protection against malaria in Aotus monkeys immunized with a recombinant blood-stage antigen fused to a universal T-cell epitope: correlation of serum gamma interferon levels with protection. Infect Immun. 1992 Jan;60(1):154–158. doi: 10.1128/iai.60.1.154-158.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herrington D. A., Losonsky G. A., Smith G., Volvovitz F., Cochran M., Jackson K., Hoffman S. L., Gordon D. M., Levine M. M., Edelman R. Safety and immunogenicity in volunteers of a recombinant Plasmodium falciparum circumsporozoite protein malaria vaccine produced in Lepidopteran cells. Vaccine. 1992;10(12):841–846. doi: 10.1016/0264-410x(92)90047-n. [DOI] [PubMed] [Google Scholar]
- Hui G. S., Chang S. P. Plasmodium falciparum: induction of biologically active antibodies to gp195 is dependent on the choice of adjuvants. Exp Parasitol. 1992 Aug;75(1):155–157. doi: 10.1016/0014-4894(92)90131-s. [DOI] [PubMed] [Google Scholar]
- Hunter R. L., Kidd M. R., Olsen M. R., Patterson P. S., Lal A. A. Induction of long-lasting immunity to Plasmodium yoelii malaria with whole blood-stage antigens and copolymer adjuvants. J Immunol. 1995 Feb 15;154(4):1762–1769. [PubMed] [Google Scholar]
- Langhorne J. The role of CD4+ T-cells in the immune response to Plasmodium chabaudi. Parasitol Today. 1989 Nov;5(11):362–364. doi: 10.1016/0169-4758(89)90113-0. [DOI] [PubMed] [Google Scholar]
- Ling I. T., Ogun S. A., Holder A. A. Immunization against malaria with a recombinant protein. Parasite Immunol. 1994 Feb;16(2):63–67. doi: 10.1111/j.1365-3024.1994.tb00324.x. [DOI] [PubMed] [Google Scholar]
- Majarian W. R., Daly T. M., Weidanz W. P., Long C. A. Passive immunization against murine malaria with an IgG3 monoclonal antibody. J Immunol. 1984 Jun;132(6):3131–3137. [PubMed] [Google Scholar]
- Nakane A., Numata A., Minagawa T. Endogenous tumor necrosis factor, interleukin-6, and gamma interferon levels during Listeria monocytogenes infection in mice. Infect Immun. 1992 Feb;60(2):523–528. doi: 10.1128/iai.60.2.523-528.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patarroyo M. E., Amador R., Clavijo P., Moreno A., Guzman F., Romero P., Tascon R., Franco A., Murillo L. A., Ponton G. A synthetic vaccine protects humans against challenge with asexual blood stages of Plasmodium falciparum malaria. Nature. 1988 Mar 10;332(6160):158–161. doi: 10.1038/332158a0. [DOI] [PubMed] [Google Scholar]
- Patarroyo M. E., Romero P., Torres M. L., Clavijo P., Moreno A., Martínez A., Rodríguez R., Guzman F., Cabezas E. Induction of protective immunity against experimental infection with malaria using synthetic peptides. Nature. 1987 Aug 13;328(6131):629–632. doi: 10.1038/328629a0. [DOI] [PubMed] [Google Scholar]
- Perlmann H., Kumar S., Vinetz J. M., Kullberg M., Miller L. H., Perlmann P. Cellular mechanisms in the immune response to malaria in Plasmodium vinckei-infected mice. Infect Immun. 1995 Oct;63(10):3987–3993. doi: 10.1128/iai.63.10.3987-3993.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Playfair J. H., De Souza J. B. Antibody responses in mice protected against malaria by vaccination. Parasite Immunol. 1979 Autumn;1(3):197–208. doi: 10.1111/j.1365-3024.1979.tb00706.x. [DOI] [PubMed] [Google Scholar]
- Playfair J. H., De Souza J. B. Vaccination of mice against malaria with soluble antigens. I. The effect of detergent, route of injection, and adjuvant. Parasite Immunol. 1986 Sep;8(5):409–414. doi: 10.1111/j.1365-3024.1986.tb00857.x. [DOI] [PubMed] [Google Scholar]
- Raychaudhuri S., Tonks M., Carbone F., Ryskamp T., Morrow W. J., Hanna N. Induction of antigen-specific class I-restricted cytotoxic T cells by soluble proteins in vivo. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8308–8312. doi: 10.1073/pnas.89.17.8308. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Riley E. M., Allen S. J., Wheeler J. G., Blackman M. J., Bennett S., Takacs B., Schönfeld H. J., Holder A. A., Greenwood B. M. Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (PfMSP1) of Plasmodium falciparum are associated with reduced malaria morbidity. Parasite Immunol. 1992 May;14(3):321–337. doi: 10.1111/j.1365-3024.1992.tb00471.x. [DOI] [PubMed] [Google Scholar]
- Snapper C. M. Regulation of murine B cell Thy-1 expression by IL-4, IFN-gamma, and CD4+ T cell subsets. Cell Immunol. 1990 Aug;129(1):80–94. doi: 10.1016/0008-8749(90)90188-w. [DOI] [PubMed] [Google Scholar]
- Stevenson M. M., Tam M. F. Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice. Clin Exp Immunol. 1993 Apr;92(1):77–83. doi: 10.1111/j.1365-2249.1993.tb05951.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stevenson M. M., Tam M. F., Wolf S. F., Sher A. IL-12-induced protection against blood-stage Plasmodium chabaudi AS requires IFN-gamma and TNF-alpha and occurs via a nitric oxide-dependent mechanism. J Immunol. 1995 Sep 1;155(5):2545–2556. [PubMed] [Google Scholar]
- Voller A., O'Neill P. Immunofluorescence method suitable for large-scale application to malaria. Bull World Health Organ. 1971;45(4):524–529. [PMC free article] [PubMed] [Google Scholar]
- Waki S., Uehara S., Kanbe K., Nariuch H., Suzuki M. Interferon-gamma and the induction of protective IgG2a antibodies in non-lethal Plasmodium berghei infections of mice. Parasite Immunol. 1995 Oct;17(10):503–508. doi: 10.1111/j.1365-3024.1995.tb00880.x. [DOI] [PubMed] [Google Scholar]
- de Souza J. B., Playfair J. H. A novel adjuvant for use with a blood-stage malaria vaccine. Vaccine. 1995 Oct;13(14):1316–1319. doi: 10.1016/0264-410x(95)00025-v. [DOI] [PubMed] [Google Scholar]
- ten Hagen T. L., Sulzer A. J., Kidd M. R., Lal A. A., Hunter R. L. Role of adjuvants in the modulation of antibody isotype, specificity, and induction of protection by whole blood-stage Plasmodium yoelii vaccines. J Immunol. 1993 Dec 15;151(12):7077–7085. [PubMed] [Google Scholar]
- von der Weid T., Kopf M., Köhler G., Langhorne J. The immune response to Plasmodium chabaudi malaria in interleukin-4-deficient mice. Eur J Immunol. 1994 Oct;24(10):2285–2293. doi: 10.1002/eji.1830241004. [DOI] [PubMed] [Google Scholar]