Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans

Suárez, Carlos F.; Pabón, Laura; Barrera, Ana María Bermejo; Aza-Conde, Jorge; Patarroyo, Manuel A.; Patarroyo, Manuel Elkín

doi:10.1016/j.bbrc.2017.08.012

Cited by 12 publications

(14 citation statements)

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“…This means that cattle have 129 distinct PBR (based on sequence identity) and that infectious disease control programmes should be designed as if there were 129 different alleles instead of 140 (136 in the IPD Database and four reported elsewhere). A similar amount of PBR sequences has been determined in humans and owl monkeys (Suarez et al, 2017). This is especially important when it comes to peptide-based vaccine design which might be more efficacious when the peptide-MHC complex has potentially greater affinity as this can be increased by modifying peptides to bind to MHC molecules [reviewed in (Patarroyo et al, 2011)].…”

Section: Discussionmentioning

confidence: 99%

“…The few MHC alleles in domestic animals contrasts with those of other species (Nino-Vasquez et al, 2000;Suarez et al, 2006;Lopez et al, 2014;Maccari et al, 2017;Shiina et al, 2017). However, a smaller amount of alleles does not necessarily mean reduced functionality, in fact two species can have very similar functional repertoire size despite varying regarding the amount of alleles (Suarez et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Major Histocompatibility Complex Class II (DRB3) Genetic Diversity in Spanish Morucha and Colombian Normande Cattle Compared to Taurine and Zebu Populations

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Major Histocompatibility Complex Class II (DRB3) Genetic Diversity in Spanish Morucha and Colombian Normande Cattle Compared to Taurine and Zebu Populations

et al. 2020

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“…Recent in-depth structural analysis has shown that any malaria vaccine component identified as highly immunogenic and protection-inducing (following challenge in immunized Aotus monkeys) can be readily used in humans without further modification [ 187 ]. Since Aotus MHCII 3D structure has not yet been described, we used well-known HLA-DRβ1* crystallographic structures to model monkey alleles.…”

Section: Chemical Features To Be Taken Into Account In Vaccine Devmentioning

confidence: 99%

Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development: A Chemical Perspective

et al. 2017

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Synthetic peptides have become invaluable biomedical research and medicinal chemistry tools for studying functional roles, i.e., binding or proteolytic activity, naturally-occurring regions’ immunogenicity in proteins and developing therapeutic agents and vaccines. Synthetic peptides can mimic protein sites; their structure and function can be easily modulated by specific amino acid replacement. They have major advantages, i.e., they are cheap, easily-produced and chemically stable, lack infectious and secondary adverse reactions and can induce immune responses via T- and B-cell epitopes. Our group has previously shown that using synthetic peptides and adopting a functional approach has led to identifying Plasmodium falciparum conserved regions binding to host cells. Conserved high activity binding peptides’ (cHABPs) physicochemical, structural and immunological characteristics have been taken into account for properly modifying and converting them into highly immunogenic, protection-inducing peptides (mHABPs) in the experimental Aotus monkey model. This article describes stereo–electron and topochemical characteristics regarding major histocompatibility complex (MHC)-mHABP-T-cell receptor (TCR) complex formation. Some mHABPs in this complex inducing long-lasting, protective immunity have been named immune protection-inducing protein structures (IMPIPS), forming the subunit components in chemically synthesized vaccines. This manuscript summarizes this particular field and adds our recent findings concerning intramolecular interactions (H-bonds or π-interactions) enabling proper IMPIPS structure as well as the peripheral flanking residues (PFR) to stabilize the MHCII-IMPIPS-TCR interaction, aimed at inducing long-lasting, protective immunological memory.

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“…[164,165]. Parasite proteins' interaction with the human immune system should be analysed by predicting B and T epitopes (using NetMHCIIpan 3.2 or other predictors) and/or in vivo evaluation in models such as the Aotus monkeys (highly susceptible to developing human malaria and having a ~ 90% identical immune system with that of humans) [166][167][168][169][170][171][172].…”

Section: Discussionmentioning

confidence: 99%

Plasmodium falciparum pre-erythrocytic stage vaccine development

Molina-Franky

Cuy-Chaparro

Camargo

et al. 2020

Malar J

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Worldwide strategies between 2010 and 2017 aimed at controlling malarial parasites (mainly Plasmodium falciparum) led to a reduction of just 18% regarding disease incidence rates. Many biologically-derived anti-malarial vaccine candidates have been developed to date; this has involved using many experimental animals, an immense amount of work and the investment of millions of dollars. This review provides an overview of the current state and the main results of clinical trials for sporozoite-targeting vaccines (i.e. the parasite stage infecting the liver) carried out by research groups in areas having variable malaria transmission rates. However, none has led to promising results regarding the effective control of the disease, thereby making it necessary to complement such efforts at finding/introducing new vaccine candidates by adopting a multi-epitope, multi-stage approach, based on minimal subunits of the main sporozoite proteins involved in the invasion of the liver.

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Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans

Cited by 12 publications

References 28 publications

Major Histocompatibility Complex Class II (DRB3) Genetic Diversity in Spanish Morucha and Colombian Normande Cattle Compared to Taurine and Zebu Populations

Major Histocompatibility Complex Class II (DRB3) Genetic Diversity in Spanish Morucha and Colombian Normande Cattle Compared to Taurine and Zebu Populations

Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development: A Chemical Perspective

Plasmodium falciparum pre-erythrocytic stage vaccine development

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