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. 1999 Feb 16;96(4):1615-20.
doi: 10.1073/pnas.96.4.1615.

Immunogenicity and in vitro protective efficacy of a recombinant multistage Plasmodium falciparum candidate vaccine

Y P Shi  1 , S E Hasnain, J B Sacci, B P Holloway, H Fujioka, N Kumar, R Wohlhueter, S L Hoffman, W E Collins, A A Lal
Affiliations

Immunogenicity and in vitro protective efficacy of a recombinant multistage Plasmodium falciparum candidate vaccine

Y P Shi et al. Proc Natl Acad Sci U S A. .

Abstract

Compared with a single-stage antigen-based vaccine, a multistage and multivalent Plasmodium falciparum vaccine would be more efficacious by inducing "multiple layers" of immunity. We have constructed a synthetic gene that encodes for 12 B cell, 6 T cell proliferative, and 3 cytotoxic T lymphocyte epitopes derived from 9 stage-specific P. falciparum antigens corresponding to the sporozoite, liver, erythrocytic asexual, and sexual stages. The gene was expressed in the baculovirus system, and a 41-kDa antigen, termed CDC/NIIMALVAC-1, was purified. Immunization in rabbits with the purified protein in the presence of different adjuvants generated antibody responses that recognized vaccine antigen, linear peptides contained in the vaccine, and all stages of P. falciparum. In vitro assays of protection revealed that the vaccine-elicited antibodies strongly inhibited sporozoite invasion of hepatoma cells and growth of blood-stage parasites in the presence of monocytes. These observations demonstrate that a multicomponent, multistage malaria vaccine can induce immune responses that inhibit parasite development at multiple stages. The rationale and approach used in the development of a multicomponent P. falciparum vaccine will be useful in the development of a multispecies human malaria vaccine and vaccines against other infectious diseases.

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Figures

Figure 1
Figure 1
Antibody responses in sera as measured by ELISA and binding of purified IgGs. (A) Rabbits were immunized with purified CDC/NII MAL VAC-1 by using different adjuvant formulations at weeks 0, 3, 6, and 9 as indicated by arrows. Antibody responses to CDC/NII MAL VAC-1 in the sera from rabbits receiving Freund’s (⋄), copolymer (■), and alum (○) were measured. Titers were determined based on the highest dilution of the samples that generated an OD greater than cutoff value (mean ± 3 SD of preimmunization sera). ODs lower than cutoff value at 1:50 dilution were considered negative responses. (B) Purified antibodies at concentration of 50 μg/ml were presented at 5 μl/min to a Biacore sensor cell loaded with CDC/NII MAL VAC-1 protein. Inset shows initial velocities of association (450–500 sec).
Figure 2
Figure 2
Ultrastructural localization of antibody reactivities with various stages of P. falciparum. Reactivities of the purified antibody from rabbit 789 receiving copolymer as adjuvant are presented here. Gold particles were found on the surface and in the cytoplasm of the sporozoite (arrows in A), in the parasitophorous vacuole membrane and cytoplasm of exoerythrocytic stage (arrows in B), in the cytoplasm in gametocyte stage III-IV (arrow in C), in rhoptry and surface of merozoite of blood stage (arrows in D), and in the cytoplasm of trophozoite of blood stage (arrow in E).
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Comment in

  • Malaria vaccines.
    Holder AA. Holder AA. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1167-9. doi: 10.1073/pnas.96.4.1167. Proc Natl Acad Sci U S A. 1999. PMID: 9989994 Free PMC article. Review. No abstract available.

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