Strategies for the development of an antimalarial vaccine

Enders, B.; Hundt, Erika; Knapp, Bernhard

doi:10.1016/0264-410x(92)90326-f

Cited by 9 publications

(11 citation statements)

References 16 publications

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“…We and others have found that use of a single vaccine antigen, such as the highly immunogenic B. bovis RAP-1 or MSA-1 protein, is not sufficient for stimulating protective immunity against B. bovis infection (28,45). On the other hand, multiepitope vaccines have been shown to induce a protective level of specific antibody and cellular immunity against experimental models of malaria and to stimulate T-lymphocyte responses in Plasmodium falciparum-vaccinated or exposed humans (21,23,32,33,46). As we have demonstrated in the present and recent studies, B. bovis Hsp20 is conserved among B. bovis strains and B. bigemina and is immunogenic for T cells in cattle with different genetic backgrounds.…”

Section: Vol 72 2004supporting

confidence: 53%

Conservation ofBabesia bovisSmall Heat Shock Protein (Hsp20) among Strains and Definition of T Helper Cell Epitopes Recognized by Cattle with Diverse Major Histocompatibility Complex Class II Haplotypes

et al. 2004

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Babesia bovis small heat shock protein (Hsp20) is recognized by CD4؉ T lymphocytes from cattle that have recovered from infection and are immune to challenge. This candidate vaccine antigen is related to a protective antigen of Toxoplasma gondii, Hsp30/bag1, and both are members of the ␣-crystallin family of proteins that can serve as molecular chaperones. In the present study, immunofluorescence microscopy determined that Hsp20 is expressed intracellularly in all merozoites. Importantly, Hsp20 is also expressed by tick larval stages, including sporozoites, so that natural tick-transmitted infection could boost a vaccine-induced response. The predicted amino acid sequence of Hsp20 from merozoites is completely conserved among different B. bovis strains. To define the location of CD4 ؉ T-cell epitopes for inclusion in a multiepitope peptide or minigene vaccine construct, truncated recombinant Hsp20 proteins and overlapping peptides were tested for their ability to stimulate T cells from immune cattle. Both amino-terminal (amino acids [aa] 1 to 105) and carboxyterminal (aa 48 to 177) regions were immunogenic for the majority of cattle in the study, stimulating strong proliferation and IFN-␥ production. T-cell lines from all individuals with distinct DRB3 haplotypes responded to aa 11 to 62 of Hsp20, which contained one or more immunodominant epitopes for each animal. One epitope, DEQTGLPIKS (aa 17 to 26), was identified by T-cell clones. The presence of strain-conserved T helper cell epitopes in aa 11 to 62 of the ubiquitously expressed Hsp20 that are presented by major histocompatibility complex class II molecules represented broadly in the Holstein breed supports the inclusion of this region in vaccine constructs to be tested in cattle.

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Section: Vol 72 2004supporting

confidence: 53%

Conservation ofBabesia bovisSmall Heat Shock Protein (Hsp20) among Strains and Definition of T Helper Cell Epitopes Recognized by Cattle with Diverse Major Histocompatibility Complex Class II Haplotypes

et al. 2004

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“…2 The p126 protein, also known as serine-rich antigen 3 or serine-rich protein 4 based on the similarity of coding genes, ranks as a candidate antigen for inclusion in a subunit vaccine to control the asexual erythrocytic phase of P. falciparum malaria for the following reasons: 1) it is antigenically conserved among different strains of P. falciparum; 5 2) monoclonal and polyclonal antibodies specific for p126 inhibit the in vitro growth of the parasite; 6-9 and 3) it can induce partial protection against parasite challenge in various species of monkeys. 1,3,[10][11][12] Moreover, the N-terminal portion (located at the amino-terminal end of the 47-kD subfragment) is involved in the induction of this protective immunity. 13,14 In view of these encouraging results, we focused on the six repeats of eight amino acids at the N-terminal end of the molecule 15 (Nt47) since this domain 1) includes a B and T cell epitope recognized by infected humans 16 (Roussilhon C, unpublished data); and 2) is the only one of the C-and Nterminal regions of the processed fragments of p126 that is able to induce an antibody response in mice immunized with respective peptides.…”

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confidence: 99%

Immune response and lack of immune response to Plasmodium falciparum P126 antigen and its amino-terminal repeat in malaria-infected humans.

Banic¹,

Oliveira-Ferreira²,

Pratt-Riccio³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. A parasitophorous vacuole protein of Plasmodium falciparum, p126, is a potential candidate for a malaria vaccine. Its N-terminal region, composed of six repeats of eight amino acids, appears to be involved in the induction of protective immunity against P. falciparum challenge in monkeys. This study evaluated the immune response to p126 and to its N-terminal region (Nt47) in patients (n ϭ 45) living in a malaria-endemic area of Brazil (Colina, Porto Velho, Rondonia). Cellular proliferative responses against Nt47 were low and infrequent. The study of the humoral immune response demonstrated that 95% of the patients had detectable anti-p126 antibodies and 77% had anti-Nt47 antibodies. Analysis of the antibody isotypes specific for Nt47 revealed that all four IgG subclasses were present and individuals with higher levels of anti-Nt47 cytophilic IgG antibody (IgG1 ϩ IgG3/IgG2 ϩ IgG4) had significantly lower parasitemia levels, suggesting that antibodies to the N-terminal region of the p126 protein may contribute to acquisition of immunity to P. falciparum malaria.The Plasmodium falciparum p126 antigen 1 is synthesized by the parasite between the 32nd and the 36th hr of a 42-hr erythrocytic cycle, then stored inside the parasitophorous vacuole. This antigen is processed into fragments of 50 and 73 kD, the latter one composed of two peptides of 47 and 18 kD linked by disulfide bridges. This processing is associated with the release of merozoites from mature schizonts. 2 The p126 protein, also known as serine-rich antigen 3 or serine-rich protein 4 based on the similarity of coding genes, ranks as a candidate antigen for inclusion in a subunit vaccine to control the asexual erythrocytic phase of P. falciparum malaria for the following reasons: 1) it is antigenically conserved among different strains of P. falciparum; 5 2) monoclonal and polyclonal antibodies specific for p126 inhibit the in vitro growth of the parasite; 6-9 and 3) it can induce partial protection against parasite challenge in various species of monkeys. 1,3,[10][11][12] Moreover, the N-terminal portion (located at the amino-terminal end of the 47-kD subfragment) is involved in the induction of this protective immunity. 13,14 In view of these encouraging results, we focused on the six repeats of eight amino acids at the N-terminal end of the molecule 15 (Nt47) since this domain 1) includes a B and T cell epitope recognized by infected humans 16 (Roussilhon C, unpublished data); and 2) is the only one of the C-and Nterminal regions of the processed fragments of p126 that is able to induce an antibody response in mice immunized with respective peptides. 17 However, mice did not develop antibodies against this domain of the molecule when immunized with schizont-infected erythrocytes. 16 It is therefore of great value for vaccine design to determine the degree of immunogenicity of the Nt47 domain in humans living in a malaria-endemic area and naturally exposed to plasmodial antigens. In this respect, we investigated the immune response to Nt47 an...

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“…This protein has the capacity to induce protection against parasite challenge in various monkey species. [1][2][3][4] Moreover, it is expressed in all isolates and is highly conserved antigenically as well as structurally. 5,6 The p126 protein, also known as serine-rich antigen 1 and serinerich protein, 7 is localized in the lumen of the parasitophorous vacuole 8 and is also found adsorbed to the surface of free merozoites.…”

Section: Introductionmentioning

confidence: 99%

Human leukocyte antigen class II control of the immune response to p126-derived amino terminal peptide from Plasmodium falciparum.

Banic¹,

Goldberg²,

Pratt-Riccio³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. We investigated the relationships between class II human leukocyte antigens (HLA) and the antibody response to Plasmodium falciparum p126 protein and to its amino-terminal portion (Nt47) in 2 malaria-endemic villages in Brazil, Colina and Ribeirinha. All people from the endemic areas had anti-p126 antibodies, and the frequencies of anti-Nt47 antibodies were similar in both communities (66% for Colina and 75% for Ribeirinha). Typing of HLA showed that Colina and Ribeirinha groups had no significant differences in HLA antigen frequencies. However, in both groups, significant associations between positive response to anti-Nt47 and presence of HLA-DR4, as well as between absence of response and presence of HLA-DR15, were observed. The predominance of positive responses to Nt47 among HLA-DR4 people was independent of the presence of any particular allele. There was no evidence for association between HLA-DQB1 alleles and antibody response to Nt47. Thus, naturally exposed people with different HLA class II antigens seem to respond differently to Nt47, indicating that the choice of relevant peptide sequences may have important consequences for subunit vaccine development.

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Strategies for the development of an antimalarial vaccine

Cited by 9 publications

References 16 publications

Conservation ofBabesia bovisSmall Heat Shock Protein (Hsp20) among Strains and Definition of T Helper Cell Epitopes Recognized by Cattle with Diverse Major Histocompatibility Complex Class II Haplotypes

Conservation ofBabesia bovisSmall Heat Shock Protein (Hsp20) among Strains and Definition of T Helper Cell Epitopes Recognized by Cattle with Diverse Major Histocompatibility Complex Class II Haplotypes

Immune response and lack of immune response to Plasmodium falciparum P126 antigen and its amino-terminal repeat in malaria-infected humans.

Human leukocyte antigen class II control of the immune response to p126-derived amino terminal peptide from Plasmodium falciparum.

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