A specific T‐cell receptor genotype preference in the immune response to a synthetic <i>Plasmodium falciparum</i> malaria vaccine

Murillo, Luis A.; Tenjo, Fernando; Clavijo, Olga P.; Orozco, Mauricio; Sampaio, Silvia; Kalil, Jorge; Patarroyo, Manuel E.

doi:10.1111/j.1365-3024.1992.tb00008.x

Cited by 22 publications

(6 citation statements)

References 20 publications

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“…Since this data, and some by other authors, clearly shows that genetic control of the immune response against malarial vaccines is mediated by these MHCII molecules, − a tripartite association was sought between these peptides’ induced immunological responses, HABPs ability to bind to purified HLA-DRβ1* molecules, and their 3D structure.…”

Section: Genetic Constraints Regarding Aotus Monkeys’ Immune Response...mentioning

confidence: 98%

“…The HLA typing of these vaccinated populations disclosed that most nonresponsive individuals harbored the HLA-DRβ1*04 genetic marker . Similarly, analysis of the TCR molecules activated by HLA-DRβ1*0401-presenting molecules revealed preferential use of TCR β chain Vβ3, Vβ10, and Vβ11 variable regions in nonresponsive individuals, suggesting that such nonresponsiveness was probably associated with an imperfect fit of this vaccine’s molecular components that hampered appropriate MHCII/pTCR complex formation.…”

Section: Genetic Constraints Regarding Aotus Monkeys’ Immune Response...mentioning

confidence: 99%

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Structural and Immunological Principles Leading to Chemically Synthesized, Multiantigenic, Multistage, Minimal Subunit-Based Vaccine Development

2011

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Section: Genetic Constraints Regarding Aotus Monkeys’ Immune Response...mentioning

confidence: 98%

Section: Genetic Constraints Regarding Aotus Monkeys’ Immune Response...mentioning

confidence: 99%

Structural and Immunological Principles Leading to Chemically Synthesized, Multiantigenic, Multistage, Minimal Subunit-Based Vaccine Development

2011

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“…3), showed very limited genetic variability and can thus be considered to be a conserved peptide with high RBC binding capacity [51]. Genetic control of immune response to SPf66 was associated with HLA-DRβ1* characteristics [52] and was highly determined by its interaction with the TCR [53], suggesting that the protective immune response was determined by an appropriate MHC II-peptide-TCR complex formation. These two seminal findings orientated our subsequent investigation in the search for a logical and rational method for developing vaccines, in depth to follow the logical approach so far adopted towards P. falciparum malaria vaccine development.…”

Section: Prior Molecular Basis Supporting the Feasibility Of A Multi-mentioning

confidence: 99%

Based on HLA-DRβ1* Allele Binding Specificities, Striking Differences in Distance and TCR Contacting Residue Orientation can be Observed in Modified Protection-Inducing Malarial Synthetic Peptides

Patarroyo

Cifuentes

Salazar

et al. 2005

CMC

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An anti-malarial vaccine is urgently needed, especially against P. falciparum which causes 2 to 3 million deaths each year, mostly in Sub-Saharan African children. This vaccine should contain molecules from the parasite's different developmental stages due to the parasite's remarkable complexity and genetic variability. The first approach using synthetic peptides from different parasite stage molecules (the SPf66 malaria vaccine) conferred limited protective efficacy in Aotus monkeys and in large field-trials carried out in different parts of the world SPf66 contains red blood cell (RBC) binding merozoite peptides for which immune responses against them are genetically controlled by HLA-DR region. Therefore, a systematic search of conserved high activity binding peptides (HABP) was undertaken aimed at using them as immunogens. However, these peptides were poorly immunogenic and had poor protection-inducing capacity against experimental challenge with a P. falciparum strain highly infective for Aotus monkeys an experimental model with an immune system quite similar to humans. Modifications were thus made to key residues to render them immunogenic and protection-inducing. These native and modified HABPs' three-dimensional structure was determined by (1)H-NMR studies and their ability in forming stable Major Histocompatibility Class II - peptide (MHCII-peptide) complexes was correlated with their ability to bind in vitro to purified HLA-DR beta1* molecules. Our experimental data suggests a correlation between modified HABPs' three-dimensional structure, HLA-DR beta1* binding preferences and their protection-inducing capacity in monkeys. Furthermore, the data presented here indicates that a synthetic peptide vaccine's three-dimensional structural features dictate both HLA-DR beta1* allele binding preference (imposing genetic restriction on the immune response) and on these vaccines' protection-inducing value. Basic knowledge of a parasite's functionally active peptides, their 3D structure and their interaction for forming the MHC II- peptide-TCR complex will thus contribute towards designing fully effective multi-component, multi-stage subunit-based malarial vaccines.

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“…There is increasing evidence that immune response to SPf66 might be genetically restricted. [28][29][30][31] Immunogenicity is being evaluated and we intend to clarify this point in the future.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical and parasitologic follow-up. Periodic visits were scheduled on days 0, 30,45,90,180,195,240, 300, 360, 450, 540, 630, and 720. Evaluation of spleen size was performed by palpation in the supine position on every vaccination day, and on days 540 and 720.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of SPf66 malaria vaccine efficacy in Brazil.

Urdaneta¹,

Prata²,

Struchiner³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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This paper reports the efficacy results of the randomized, placebo-controlled, field trial of SPf66 malaria vaccine in Costa Marques, Rondonia, Brazil. This region is characterized by the seasonal distribution of Plasmodium falciparum and P. vivax infections, and the recent occupation by migrants from nonendemic areas. A total of 800 individuals of both sexes, ranging in age from seven to 60 years, were included in the study. Of the initial cohort, 572 participants completed the vaccination schedule. Clinical and parasitologic evaluations were obtained by active and passive searches on a periodic basis. The overall protective efficacy against P. falciparum infections was Ϫ1.6% (Ϫ32.9% to 22.4%), and 14.1% (Ϫ17.0% to 36.9%) for the first episode. The overall protective efficacy for P. vivax infections was Ϫ19.7% (Ϫ44.8% to 1.03%), and Ϫ10.8% (Ϫ41.1% to 12.8%) for the first episode. No statistical evidence of an overall significant protective effect of SPf66 malaria vaccine against P. falciparum and P. vivax malaria was obtained in this trial. * IDv and IDp ϭ incidence density rates in the vaccinated and placebo groups. † VE (%) ϭ vaccine efficacy estimates; CI ϭ confidence interval.

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A specific T‐cell receptor genotype preference in the immune response to a synthetic Plasmodium falciparum malaria vaccine

Cited by 22 publications

References 20 publications

Structural and Immunological Principles Leading to Chemically Synthesized, Multiantigenic, Multistage, Minimal Subunit-Based Vaccine Development

Structural and Immunological Principles Leading to Chemically Synthesized, Multiantigenic, Multistage, Minimal Subunit-Based Vaccine Development

Based on HLA-DRβ1* Allele Binding Specificities, Striking Differences in Distance and TCR Contacting Residue Orientation can be Observed in Modified Protection-Inducing Malarial Synthetic Peptides

Evaluation of SPf66 malaria vaccine efficacy in Brazil.

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A specific T‐cell receptor genotype preference in the immune response to a synthetic Plasmodium falciparum malaria vaccine

Cited by 22 publications

References 20 publications

Structural and Immunological Principles Leading to Chemically Synthesized, Multiantigenic, Multistage, Minimal Subunit-Based Vaccine Development

Structural and Immunological Principles Leading to Chemically Synthesized, Multiantigenic, Multistage, Minimal Subunit-Based Vaccine Development

Based on HLA-DR&#946;1* Allele Binding Specificities, Striking Differences in Distance and TCR Contacting Residue Orientation can be Observed in Modified Protection-Inducing Malarial Synthetic Peptides

Evaluation of SPf66 malaria vaccine efficacy in Brazil.

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Product

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Based on HLA-DRβ1* Allele Binding Specificities, Striking Differences in Distance and TCR Contacting Residue Orientation can be Observed in Modified Protection-Inducing Malarial Synthetic Peptides