Variant- and strain-specific immunity in Saimiri infected with Plasmodium falciparum.

Abstract

Abstract. Variant-and strain-specific immunity to malaria in Saimiri monkeys infected with homologous O and R variants of the Palo Alto strain (FUPSP) of Plasmodium falciparum or by various heterologous divergent strains were studied. Following homologous reinfections, the primary immune response in monkeys was effective only against the same variant type but not against the other variant, which differed only by antigens exposed at the surface of the infected red blood cell. In contrast, after two successive inoculations with a single variant type, a variant transcending immunity developed to both O and R parasite populations. The immunity against FUPSP in monkeys repeatedly infected with various combinations of heterologous strains, including Sal I, Tanzania, Camp, FUPCP, FCH4, FVO, and FUPCDC parasites was less effective, resulting at best in protecting the monkey against fulminating infection. However, in several cases, previous or concomitant heterologous infections modified the course of virulent infection by FUPSP parasites, indicating a significant degree of cross-protection between the strains. Therefore, in this model, while variant-and strain-specific antigens are important components of acquired immunity to malaria, the monkey immune response to infection transcends phenotypic antigenic variation and strain diversity.Immunity to malaria in humans is poorly protective and only acquired slowly after several years of exposure to intense transmission. It is a nonsterile immunity and requires frequent boosting if it is to last. 1 Malaria parasites exhibit an extensive antigenic polymorphism as a result of two major factors, allelic diversity and antigenic variation. While antigenic diversity and host adaptation to it are likely to be important parameters to naturally acquired immunity to malaria, little is known about the relationship between antigenic diversity and the protective immune response against infection. 2 It has been suggested that the various allelic forms of genes interfere with and hinder the development of an efficient immune response such that protection is only achieved after exposure to a large number of antigenically distinct parasite strains. 3,4 However, epidemiologic studies are not conclusive on this issue because of the complexity of natural parasite populations, host genetic diversity, and the possible presence of other immune evasion mechanisms such as antigenic variation. [5][6][7][8] It is important to determine the effect of phenotypic variation and antigenic diversity on the development of immunity. This question should be easier to address in experimental models in which the infection is well characterized and controlled. By using different approaches (parasitologic, immunologic, and molecular), we studied the relative importance of conserved and polymorphic antigenic determinants in inducing an effective immunity against Plasmodium falciparum in a monkey model. In this communication, we report the pattern of infections of Saimiri monkeys successively injected with various c...

Induction of Strain-Transcending Immunity againstPlasmodium chabaudi adamiMalaria with a Multiepitope DNA Vaccine

“…This is consistent with the observation that MSP4/5 sequences from strains of P. yoelii, recently shown to be conserved within P. yoelii, induced cross-protection against heterologous P. yoelii challenge: however, less cross-protection was observed with MSP4/5 from P. berghei against P. yoelii challenge (20). Cross-protection following exposure to P. falciparum strains is also described (7,17,26). We suggest that a multiepitope or polyprotein-based cross-protective blood-stage vaccine could feasibly be engineered for delivery in a DNA prime-virus boost approach as described for liver stage vaccines (38,45).…”

Immunization of Saimiri sciureus Monkeys with a Recombinant Hybrid Protein Derived from the Plasmodium falciparum Antigen Glutamate-Rich Protein and Merozoite Surface Protein 3 Can Induce Partial Protection with Freund and Montanide ISA720 Adjuvants

“…Thus, an experimental P. falciparum infection can boost vaccine-induced antibody responses. It is In the present study, we did not perform a second challenge to examine the effect of a natural boost on protection because Saimiri monkeys become largely resistant to homologous challenge after one infection (6).…”

Identification of T Cell Epitopes on the 33-kDa Fragment of Plasmodium yoelii Merozoite Surface Protein 1 and Their Antibody-Independent Protective Role in Immunity to Blood Stage Malaria

“…Immunity to malaria is commonly species, stage, strain, and variant specific (22)(23)(24). Thus, an ideal malaria vaccine should comprise multiple epitopes that would cover various stages of the complex life cycle and induce cross-protection against many strains.…”