Abstract
The efficacy of a whole-sporozoite malaria vaccine would partly be determined by the strain-specificity of the protective responses against malarial sporozoites and liver-stage parasites. Evidence from previous reports were inconsistent, where some studies have shown that the protective immunity induced by irradiated or live sporozoites in rodents or humans were cross-protective and in others strain-specific. In the present work, we have studied the strain-specificity of live sporozoite-induced immunity using two genetically and immunologically different strains of Plasmodium cynomolgi, Pc746 and PcCeylon, in toque monkeys. Two groups of monkeys were immunized against live sporozoites of either the Pc746 (n = 5), or the PcCeylon (n = 4) strain, by the bites of 2–4 sporozoite-infected Anopheles tessellates mosquitoes per monkey under concurrent treatments with chloroquine and primaquine to abrogate detectable blood infections. Subsequently, a group of non-immunized monkeys (n = 4), and the two groups of immunized monkeys were challenged with a mixture of sporozoites of the two strains by the bites of 2–5 infective mosquitoes from each strain per monkey. In order to determine the strain-specificity of the protective immunity, the proportions of parasites of the two strains in the challenge infections were quantified using an allele quantification assay, Pyrosequencing™, based on a single nucleotide polymorphism (SNP) in the parasites’ circumsporozoite protein gene. The Pyrosequencing™ data showed that a significant reduction of parasites of the immunizing strain in each group of strain-specifically immunized monkeys had occurred, indicating a stronger killing effect on parasites of the immunizing strain. Thus, the protective immunity developed following a single, live sporozoite/chloroquine immunization, acted specifically against the immunizing strain and was, therefore, strain-specific. As our experiment does not allow us to determine the parasite stage at which the strain-specific protective immunity is directed, it is possible that the target of this immunity could be either the pre-erythrocytic stage, or the blood-stage, or both.
Highlights
One of the approaches for developing an effective anti-malaria vaccine is to induce a protective immune response by vaccination with whole parasites [1]
Our results indicate that strain-specific protective immunity had been induced by a single immunization with live P. cynomolgi sporozoites under the cover of drugs that prevented active blood infection
Malaria-free toque monkeys were immunized by the bites of An. tessellates mosquitoes infected with live sporozoites of either of the two P. cynomolgi strains, Pc746 or PcCeylon
Summary
One of the approaches for developing an effective anti-malaria vaccine is to induce a protective immune response by vaccination with whole parasites [1]. The efficacy of a whole sporozoite vaccine, as of any other, will partly depend upon the degree of diversity of the genes that code for target antigens of vaccine-induced immunity [8,9,10,11] This diversity may lead to parasite strain- or genotype-specific protective immune responses that would limit the degree of cross-protection to different parasite strains. Experiments with P. cynomolgi in hepatocyte cultures [15] and P. chabaudi in mice [16] showed evidence for strain-specific responses against PE stages In most of these studies involving animals or human subjects, the degree of strain-specific protection was determined by the parasitological response following homologous or heterologous challenge in the immunized host. Our results indicate that strain-specific protective immunity had been induced by a single immunization with live P. cynomolgi sporozoites under the cover of drugs that prevented active blood infection
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