Vaccination with novel immunostimulatory adjuvants against blood-stage malaria in mice.
An important aspect of malaria vaccine development is the identification of an appropriate adjuvant which is both capable of stimulating a protective immune response and safe for use by humans. Here, we investigated the feasibility of using novel immunostimulatory molecules as adjuvants combined with a crude antigen preparation and coadsorbed to aluminum hydroxide (alum) as a vaccine against blood-stage Plasmodium chabaudi AS malaria. Prior to challenge infection, immunization of genetically susceptible A/J mice with the combination of malaria antigen plus recombinant interleukin-12 (IL-12) in alum induced a Th1 immune response with production of high levels of gamma interferon (IFN-gamma) and diminished IL-4 levels by spleen cells stimulated in vitro with parasite antigen compared to mice immunized with antigen alone, antigen in alum, or antigen plus IL-12. Mice immunized with malaria antigen plus recombinant IL-12 in alum had high levels of total malaria-specific antibody and immunoglobulin G2a. Compared to unimmunized mice, immunization with antigen plus IL-12 in alum induced the highest level of protective immunity against challenge infection with P. chabaudi AS, which was evident as a significantly decreased peak parasitemia level and 100% survival. Protective immunity was dependent on CD4(+) T cells, IFN-gamma, and B cells and was long-lasting. Replacement of IL-12 as an adjuvant by synthetic oligodeoxynucleotides (ODN) containing CpG motifs induced a similar level of vaccine-induced protection against challenge infection with P. chabaudi AS. These results illustrate that it is possible to enhance the potency of a crude malaria antigen preparation delivered in alum by inclusion of immunostimulatory molecules, such as IL-12 or CpG-ODN.
Su
Zhong
Z
Centre for the Study of Host Resistance, McGill University Health Centre Research Institute, McGill University, Montreal, Quebec, Canada.
Tam
Mi-Fong
MF
Jankovic
Dragana
D
Stevenson
Mary M
MM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D018664:Interleukin-12 / Q000008:administration & dosage; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D016788:Plasmodium chabaudi / Q000276:immunology / Q000472:pathogenicity; D011994:Recombinant Proteins / Q000008:administration & dosage; D018417:Th1 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; C408982:CPG-oligonucleotide; D017780:Malaria Vaccines; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D018664:Interleukin-12; C041524:aluminum sulfate; D007371:Interferon-gamma