CpG oligodeoxynucleotide enhances immunity against blood-stage malaria infection in mice parenterally immunized with a yeast-expressed 19 kDa carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (MSP119) formulated in oil-based Montanides

Hirunpetcharat, Chakrit; Wipasa, Jiraprapa; Sakkhachornphop, Supachai; Nitkumhan, T.; Zheng, Yan-Peng; Pichyangkul, Sathit; Krieg, Arthur Μ.; Walsh, Douglas S.; Heppner, D. Gray; Good, Michael F.

doi:10.1016/s0264-410x(03)00132-4

Cited by 45 publications

(35 citation statements)

References 33 publications

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“…For blood-stage malaria, numerous approaches have been pursued, including the use of subunit antigens, prime-boost strategies, or combination of adjuvants to induce robust humoral responses. Here, we report on what we believe to be a novel T cell vaccine against blood-stage malaria that builds on previous observations that (a) IL-12 and ODN are effective adjuvants for immunization against blood-stage infection (33,34) and (b) low doses of antigenic stimulus facilitate cellular immunity. We combined these strategies with a whole-parasite approach to demonstrate that administration of extremely low doses of killed blood-stage parasites in CpG-ODN is able to engender broad protection against lethal blood-stage challenge through the generation of cross-reactive T cells.…”

Section: Discussionmentioning

confidence: 90%

Low doses of killed parasite in CpG elicit vigorous CD4+ T cell responses against blood-stage malaria in mice

Pinzón-Charry

McPhun²,

Kienzle³

et al. 2010

J. Clin. Invest.

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Development of a vaccine that targets blood-stage malaria parasites is imperative if we are to sustainably reduce the morbidity and mortality caused by this infection. Such a vaccine should elicit long-lasting immune responses against conserved determinants in the parasite population. Most blood-stage vaccines, however, induce protective antibodies against surface antigens, which tend to be polymorphic. Cell-mediated responses, on the other hand, offer the theoretical advantage of targeting internal antigens that are more likely to be conserved. Nonetheless, few of the current blood-stage vaccine candidates are able to harness vigorous T cell immunity. Here, we present what we believe to be a novel blood-stage whole-organism vaccine that, by combining low doses of killed parasite with CpG-oligodeoxynucleotide (CpG-ODN) adjuvant, was able to elicit strong and cross-reactive T cell responses in mice. Our data demonstrate that immunization of mice with 1,000 killed parasites in CpG-ODN engendered durable and cross-strain protection by inducing a vigorous response that was dependent on CD4 + T cells, IFN-γ, and nitric oxide. If applicable to humans, this approach should facilitate the generation of robust, cross-reactive T cell responses against malaria as well as antigen availability for vaccine manufacture.

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Section: Discussionmentioning

confidence: 90%

Low doses of killed parasite in CpG elicit vigorous CD4+ T cell responses against blood-stage malaria in mice

Pinzón-Charry

McPhun²,

Kienzle³

et al. 2010

J. Clin. Invest.

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“…of GST as a heterologous carrier could be eliminated by inclusion of other heterologous T cell epitopes (52,53) or by 4 to 5 immunizations with nonfused PyMSP-1 19 emulsified in potent adjuvants, including CFA/IFA (37,54) or M plus CpG ODN (55)(56)(57). We are unaware of any studies where immunization with nonfused, recombinant PyMSP-1 42 demonstrated comparable protective efficacy.…”

Section: Discussionmentioning

confidence: 99%

A Chimeric Plasmodium falciparum Merozoite Surface Protein Vaccine Induces High Titers of Parasite Growth Inhibitory Antibodies

et al. 2013

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The C-terminal 19-kDa domain of Plasmodium falciparum merozoite surface protein 1 (PfMSP1 19 ) is an established target of protective antibodies. However, clinical trials of PfMSP1 42 , a leading blood-stage vaccine candidate which contains the protective epitopes of PfMSP1 19 , revealed suboptimal immunogenicity and efficacy. Based on proof-of-concept studies in the Plasmodium yoelii murine model, we produced a chimeric vaccine antigen containing recombinant PfMSP1 19 (rPfMSP1 19 ) fused to the N terminus of P. falciparum merozoite surface protein 8 that lacked its low-complexity Asn/Asp-rich domain, rPfMSP8 (⌬Asn/ Asp). Immunization of mice with the chimeric rPfMSP1/8 vaccine elicited strong T cell responses to conserved epitopes associated with the rPfMSP8 (⌬Asn/Asp) fusion partner. While specific for PfMSP8, this T cell response was adequate to provide help for the production of high titers of antibodies to both PfMSP1 19 and rPfMSP8 (⌬Asn/Asp) components. This occurred with formulations adjuvanted with either Quil A or with Montanide ISA 720 plus CpG oligodeoxynucleotide (ODN) and was observed in both inbred and outbred strains of mice. PfMSP1/8-induced antibodies were highly reactive with two major alleles of PfMSP1 19 (FVO and 3D7). Of particular interest, immunization with PfMSP1/8 elicited higher titers of PfMSP1 19 -specific antibodies than a combined formulation of rPfMSP1 42 and rPfMSP8 (⌬Asn/Asp). As a measure of functionality, PfMSP1/8-specific rabbit IgG was shown to potently inhibit the in vitro growth of blood-stage parasites of the FVO and 3D7 strains of P. falciparum. These data support the further testing and evaluation of this chimeric PfMSP1/8 antigen as a component of a multivalent vaccine for P. falciparum malaria.

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“…Activation of dendritic cells by CpG ODN induces cell maturation and production of proinflammatory cytokines, such as interleukin 1 (IL-1), IL-6, tumor necrosis factor alpha, and type I interferon, as well as Th1-promoting cytokine IL-12 (1,25). CpG ODNs have been found to be useful as adjuvants for peptide/protein vaccines against various pathogens, including malaria parasite antigens (13,16,19,26). The results of our previous studies have demonstrated that CpG ODN in combination with Montanide ISA51 or ISA720 strongly promotes MSP1 19 in induction of specific antibody response and protection against a lethal malaria infection in mice (13).…”

mentioning

confidence: 99%

Long-Lasting Protective Immune Response to the 19-Kilodalton Carboxy-Terminal Fragment ofPlasmodium yoeliiMerozoite Surface Protein 1 in Mice

Jeamwattanalert

Mahakunkijcharoen

Kittigul

et al. 2007

Clin Vaccine Immunol

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CpG oligodeoxynucleotide enhances immunity against blood-stage malaria infection in mice parenterally immunized with a yeast-expressed 19 kDa carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (MSP119) formulated in oil-based Montanides

Cited by 45 publications

References 33 publications

Low doses of killed parasite in CpG elicit vigorous CD4+ T cell responses against blood-stage malaria in mice

Low doses of killed parasite in CpG elicit vigorous CD4+ T cell responses against blood-stage malaria in mice

A Chimeric Plasmodium falciparum Merozoite Surface Protein Vaccine Induces High Titers of Parasite Growth Inhibitory Antibodies

Long-Lasting Protective Immune Response to the 19-Kilodalton Carboxy-Terminal Fragment ofPlasmodium yoeliiMerozoite Surface Protein 1 in Mice

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