Attenuated vaccinia virus-circumsporozoite protein recombinants confer protection against rodent malaria

Lanar, David E.; Tine, John A.; Taisne, C. de; Seguin, M C; Cox, William I.; Winslow, Joseph P.; Ware, Lisa A.; Kauffman, Elizabeth B.; Gordon, Daniel M.; Ballou, W. Ripley; Paoletti, Enzo; Sadoff, Jerald C.

doi:10.1128/iai.64.5.1666-1671.1996

Cited by 38 publications

(11 citation statements)

References 55 publications

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“…Recombinant vaccinia viruses. Recombinant poxviruses were produced in collaboration with Virogenetics Corporation (Troy, N.Y.) (24,42 Immunization regimen. Fifteen malaria-naive rhesus monkeys (Macaca mulata), age 1 to 1.5 years and weighing 1.5 to 3 kg, were randomized into five groups of three monkeys per group (Table 1).…”

Section: Methodsmentioning

confidence: 99%

Simultaneous Induction of Multiple Antigen-Specific Cytotoxic T Lymphocytes in Nonhuman Primates by Immunization with a Mixture of Four Plasmodium falciparum DNA Plasmids

et al. 1998

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CD8 ؉ T cells have been implicated as critical effector cells in protective immunity against malaria parasites developing within hepatocytes. A vaccine that protects against malaria by inducing CD8 ؉ T cells will probably have to include multiple epitopes on the same protein or different proteins, because of parasite polymorphism and genetic restriction of T-cell responses. To determine if CD8؉ T-cell responses against multiple P. falciparum proteins can be induced in primates by immunization with plasmid DNA, rhesus monkeys were immunized intramuscularly with a mixture of DNA plasmids encoding four P. falciparum proteins or with individual plasmids. All six monkeys immunized with PfCSP DNA, seven of nine immunized with PfSSP2 DNA, and five of six immunized with PfExp-1 or PfLSA-1 DNA had detectable antigen-specific cytotoxic T lymphocytes (CTL) after in vitro restimulation of peripheral blood mononuclear cells. CTL activity was genetically restricted and dependent on CD8 ؉ T cells. By providing the first evidence for primates that immunization with a mixture of DNA plasmids induces CD8 ؉ T-cell responses against all the components of the mixture, these studies provide the foundation for multigene immunization of humans.

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Section: Methodsmentioning

confidence: 99%

Simultaneous Induction of Multiple Antigen-Specific Cytotoxic T Lymphocytes in Nonhuman Primates by Immunization with a Mixture of Four Plasmodium falciparum DNA Plasmids

et al. 1998

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“…One rationale for developing a poxvirus-based vaccine was to maximize the elicitation of cellular immunity, particularly CTL responses (45). The inclusion of at least five antigens expressed during the liver stage of parasite development (25,66,77), and probably a sixth (AMA1), provides NYVAC-Pf7 with the potential to direct a broad-based CTL response against infected liver cells.…”

Section: Discussionmentioning

confidence: 99%

“…In some studies, these antigens have been shown to provide a level of protection in experimental models of malaria infection. CSP and SSP2 elicit protective immune responses, particularly cellular responses mediated by CD8 ϩ T cells (1,45,46,57,67,70,72), in rodents. Although CSPbased vaccine candidates evaluated in human clinical trials have provided disappointing results (2,30), the tested vaccines have in general been designed to elicit humoral rather than cellular responses.…”

Section: Fig 3 Cell Surface Expression Of P Falciparum Antigens Bymentioning

confidence: 99%

“…not diminish its immunizing potential as a vector in experimental or target species (5,14,43,78,80). In contrast to the failure of other vaccinia virus-malaria recombinants (46,64,68,71), the potential of NYVAC-based recombinants to confer pro-tection from experimental challenge with malaria parasites has been demonstrated (45). NYVAC thus provides a suitable foundation for the development of a multiantigen, multistage vaccine for human malaria.…”

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confidence: 99%

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NYVAC-Pf7: a poxvirus-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria

et al. 1996

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The highly attenuated NYVAC vaccinia virus strain has been utilized to develop a multiantigen, multistage vaccine candidate for malaria, a disease that remains a serious global health problem and for which no highly effective vaccine exists. Genes encoding seven Plasmodium falciparum antigens derived from the sporozoite (circumsporozoite protein and sporozoite surface protein 2), liver (liver stage antigen 1), blood (merozoite surface protein 1, serine repeat antigen, and apical membrane antigen 1), and sexual (25-kDa sexual-stage antigen) stages of the parasite life cycle were inserted into a single NYVAC genome to generate NYVAC-Pf7. Each of the seven antigens was expressed in NYVAC-Pf7-infected culture cells, and the genotypic and phenotypic stability of the recombinant virus was demonstrated. When inoculated into rhesus monkeys, NYVAC-Pf7 was safe and well tolerated. Antibodies that recognize sporozoites, liver, blood, and sexual stages of P. falciparum were elicited. Specific antibody responses against four of the P. falciparum antigens (circumsporozoite protein, sporozoite surface protein 2, merozoite surface protein 1, and 25-kDa sexual-stage antigen) were characterized. The results demonstrate that NYVAC-Pf7 is an appropriate candidate vaccine for further evaluation in human clinical trials.

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“…Previous efforts aimed at inducing protection in humans by using different CS protein-based vaccines have failed or resulted in incomplete protection (4,6,26,30). Plasmid DNA (3,15,18,20) and attenuated recombinant poxvirus vectors (2,23,35) are also being employed in the effort to generate effective malaria vaccines. The availability of gene transfer technology for the protozoan parasite Toxoplasma gondii may offer an additional opportunity to express and deliver the CS protein in a highly immunogenic form.…”

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confidence: 99%

TransformedToxoplasma gondiiTachyzoites Expressing the Circumsporozoite Protein ofPlasmodium knowlesiElicit a Specific Immune Response in Rhesus Monkeys

et al. 1999

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Toxoplasma gondii tachyzoites were transformed with the coding sequence of the circumsporozoite (CS) protein of the primate malaria parasite Plasmodium knowlesi. A single inoculation of live transformed tachyzoites elicited an antibody response directed against the immunodominant repeat epitope (EQPAAGAGG) 2 of the P. knowlesi CS protein in rhesus monkeys. Notably, these animals failed to show a positive serum conversion against T. gondii. Antibodies against Toxoplasma antigens were detected only after a second inoculation with a higher number of transformed tachyzoites. This boost induced an increased antibody response against the P. knowlesi CS protein associated with immunoglobulin class switching, thus demonstrating the establishment of immunological memory. These results indicate that the Toxoplasma-derived CS protein is efficiently recognized by the monkey immune system and represents an immunodominant antigen in transformed parasites.

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Attenuated vaccinia virus-circumsporozoite protein recombinants confer protection against rodent malaria

Cited by 38 publications

References 55 publications

Simultaneous Induction of Multiple Antigen-Specific Cytotoxic T Lymphocytes in Nonhuman Primates by Immunization with a Mixture of Four Plasmodium falciparum DNA Plasmids

Simultaneous Induction of Multiple Antigen-Specific Cytotoxic T Lymphocytes in Nonhuman Primates by Immunization with a Mixture of Four Plasmodium falciparum DNA Plasmids

NYVAC-Pf7: a poxvirus-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria

TransformedToxoplasma gondiiTachyzoites Expressing the Circumsporozoite Protein ofPlasmodium knowlesiElicit a Specific Immune Response in Rhesus Monkeys

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