EFisioTrack System for Monitoring Therapeutic Exercises in Patients with Shoulder Orthopedic Injuries in a Hospital Setting: A Pilot Feasibility Study.

To assess the effects of the eFisioTrack monitoring system on clinical variables in patients with prescribed physiotherapy for shoulder injuries, twenty-four adult patients with shoulder orthopaedic injuries who underwent physical therapy treatment in a hospital setting participated in the study (twelve in the experimental group and twelve as controls). Clinical outcome measures were shoulder function and pain (Constant-Murley Score and Disabilities of the Arm, Shoulder, and Hand or DASH score). Each variable was measured by a blinded physiotherapist at baseline and at one month follow-up. Patients performed the prescribed exercises either supervised by the physiotherapist (control group) or in a separate room without therapist supervision (experimental group). There were no statistically significant differences between groups before treatment or at follow-up for any outcomes (p ≥ 0.05). There was a statistically significant decrease (p ≤ 0.05) of at least 10 points in both groups for the DASH score at follow-up. Differences in the total score and subjective components of the Constant-Murley were also evidenced within groups. The use of the eFisioTrack system showed similar results in clinical measures compared to those performed under the direct supervision of the physiotherapist. This approach might be suitable for providing an effective shoulder exercise program at home.

Intra-observer reproducibility and inter-observer agreement of Fels skeletal age assessments among male tennis players 8-16 years.

BACKGROUND: Skeletal age (SA) is an estimate of biological maturity status that is commonly used in sport-related medical examinations. This study considered intra-observer reproducibility and inter-observer agreement of SA assessments among male tennis players. METHODS: SA was assessed with the Fels method in 97 male tennis players with chronological ages (CA) spanning 8.7-16.8 years. Radiographs were evaluated by two independent trained observers. Based on the difference between SA and CA, players were classified as late, average or early maturing; if a player was skeletally mature, he was noted as such as an SA is not assigned. RESULTS: The magnitude of intra-individual differences between repeated SA assessments were d = 0.008 year (observer A) and d = 0.001 year (observer B); the respective coefficients of variation were 1.11% and 1.75%. Inter-observer mean differences were negligible (t = 1.252, p = 0.210) and the intra-class correlation coefficient was nearly perfect (ICC = 0.995). Concordance of classifications of players by maturity status between observers was 90%. CONCLUSION: Fels SA assessments were highly reproducible and showed an acceptable level of inter-observer agreement between trained examiners. Classifications of players by skeletal maturity status based on assessments of the two observers were highly concordant, though not 100%. The results highlight the importance of experienced observers in skeletal maturity assessments.

Nitric oxide sensing in plants is mediated by proteolytic control of group VII ERF transcription factors.

Nitric oxide (NO) is an important signaling compound in prokaryotes and eukaryotes. In plants, NO regulates critical developmental transitions and stress responses. Here, we identify a mechanism for NO sensing that coordinates responses throughout development based on targeted degradation of plant-specific transcriptional regulators, the group VII ethylene response factors (ERFs). We show that the N-end rule pathway of targeted proteolysis targets these proteins for destruction in the presence of NO, and we establish them as critical regulators of diverse NO-regulated processes, including seed germination, stomatal closure, and hypocotyl elongation. Furthermore, we define the molecular mechanism for NO control of germination and crosstalk with abscisic acid (ABA) signaling through ERF-regulated expression of ABSCISIC ACID INSENSITIVE5 (ABI5). Our work demonstrates how NO sensing is integrated across multiple physiological processes by direct modulation of transcription factor stability and identifies group VII ERFs as central hubs for the perception of gaseous signals in plants.

Assessment of skeletal age in youth female soccer players: Agreement between Greulich-Pyle and Fels protocols.

OBJECTIVE: The purpose of the study was to evaluate the agreement between the Fels and Greulich-Pyle methods for the assessment of skeletal age (SA) in female youth soccer players. METHODS: The sample included 441 Portuguese players 10.08-16.73 years of age who regularly participated in organized and competitive soccer. Standardized radiographs of the left hand-wrist were obtained and analyzed by an experienced examiner. SA was estimated with the Fels and Greulich-Pyle (GP) methods. Differences between SA and chronological age (CA) were used to define skeletal maturity groups: late, average and early maturing. In addition to descriptive statistics, Cohen's kappa and Lin concordance correlation coefficients were used to evaluate agreement between methods. RESULTS: Intraindividual differences in SA based on the two methods varied between 0.10 to 1.47 years among age groups with larger mean differences at older ages. Agreement of maturity classifications between methods was 74% at younger ages (under-13: kappa = 0.48; under-14: kappa = 0.39; Lin CCC = 0.68) and declined with increasing CA (under-17: 19% agreement; kappa = 0.001; Lin CCC = 0.11). About 19% of the total sample was skeletally mature with the Fels method and an SA was not assigned; in contrast, no players were skeletally mature with the GP method. CONCLUSIONS: GP SAs were systematically lower than Fels SAs among female soccer players. Intraindividual variability in SAs between methods was considerable. The findings highlight the impact of method on estimates of maturity status.

The molecular basis for peptide-based antimalarial vaccine development targeting erythrocyte invasion by P. falciparum.

This work describes a methodology for developing a minimal, subunit-based, multi-epitope, multi-stage, chemically-synthesised, anti-Plasmodium falciparum malaria vaccine. Some modified high activity binding peptides (mHABPs) derived from functionally relevant P. falciparum MSP, RH5 and AMA-1 conserved amino acid regions (cHABPs) for parasite binding to and invasion of red blood cells (RBC) were selected. They were highly immunogenic as assessed by indirect immunofluorescence (IFA) and Western blot (WB) assays and protective immune response-inducers against malarial challenge in the Aotus monkey experimental model. NetMHCIIpan 4.0 was used for predicting peptide-Aotus/human major histocompatibility class II (MHCII) binding affinity in silico due to the similarity between Aotus and human immune system molecules; ∼50% of Aotus MHCII allele molecules have a counterpart in the human immune system, being Aotus-specific, whilst others enabled recognition of their human counterparts. Some peptides' 1H-NMR-assessed structural conformation was determined to explain residue modifications in mHABPs inducing secondary structure changes. These directly influenced immunological behaviour, thereby highlighting the relationship with MHCII antigen presentation. The data obtained in such functional, immunological, structural and predictive approach suggested that some of these peptides could be excellent components of a fully-protective antimalarial vaccine.

Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases.

Malaria remains a large-scale public health problem, killing more than 400,000 people and infecting up to 230 million worldwide, every year. Unfortunately, despite numerous efforts and research concerning vaccine development, results to date have been low and/or strain-specific. This work describes a strategy involving Plasmodium falciparum Duffy binding-like (DBL) and reticulocyte-binding protein homologue (RH) family-derived minimum functional peptides, netMHCIIpan3.2 parental and modified peptides' in silico binding prediction and modeling some Aotus major histocompatibility class II (MHCII) molecules based on known human molecules' structure to understand their differences. These are used to explain peptides' immunological behaviour when used as vaccine components in the Aotus model. Despite the great similarity between human and Aotus immune system molecules, around 50% of Aotus allele molecules lack a counterpart in the human immune system which could lead to an Aotus-specific vaccine. It was also confirmed that functional Plasmodium falciparum' conserved proteins are immunologically silent (in both the animal model and in-silico prediction); they must therefore be modified to elicit an appropriate immune response. Some peptides studied here had the desired behaviour and can thus be considered components of a fully-protective antimalarial vaccine.

Reproducibility and inter-observer agreement of Greulich-Pyle protocol to estimate skeletal age among female adolescent soccer players.

BACKGROUND: Skeletal age (SA) is considered the best method of assessing biological maturation. The aim of this study was to determine intra-observer (reproducibility) and inter-observer agreement of SA values obtained via the Greulich-Pyle (GP) method. In addition, the variation in calculated SAs by alternative GP protocols was examined. METHODS: The sample was composed of 100 Portuguese female soccer players aged 12.0-16.7 years. SAs were determined using the GP method by two observers (OB1: experience < 100 exams using GP; OB2: experience > 2000 exams using several methods). The radiographs were examined using alternative GP protocols: (wholeGP) the plate was matched to the atlas as an overall approach; (30-boneGP) bone-by-bone inspections of 30-bones; (GPpmb) bone-by-bone inspections of the pre-mature bones only. For the 30-boneGP and GPpmb approaches, SA was calculated via the mean (M) and the median (Md). RESULTS: Reproducibility ranged 82-100% and 88-100% for OB1 and OB2, respectively. Inter-observer agreement (100 participants multiplied by 30 bones) was 92.1%. For specific bones, agreement rates less than 90% were found for scaphoid (81%), medial phalange V (83%), trapezium (84%) and metacarpal V (87%). Differences in wholeGP SAs obtained by the two observers were moderate (d-cohen was 0.79). Mean differences between observers when using bone-by bone SAs were trivial (30-boneGP: d-cohen less than 0.05; GPpmb: d-cohen less than 0.10). The impact of using the mean or the median was negligible, particularly when analyses did not include bones scored as mature. CONCLUSION: The GP appeared to be a reasonably reproducible method to assess SA and inter-observer agreement was acceptable. There is evidence to support a recommendation of only scoring pre-mature bones during later adolescence. Further research is required to examine whether these findings are consistent in younger girls and in boys.

Scaling left ventricular mass in adolescent female soccer players.

BACKGROUND: The aim of the study was to examine the contribution of chronological age (CA), skeletal maturation, training experience and concurrent body size descriptors, to inter-individual variance in left ventricular mass (LVM) among female adolescent soccer players. METHODS: The sample included 228 female soccer players 11.8-17.1 years. Training experience defined as years of participation in competitive soccer (range 2-9 years), was obtained by interview. Stature, body mass and skinfolds (triceps, medial calf) were measured. Fat mass was estimated; Fat-free mass was derived. LVM was assessed by echocardiography. Skeletal maturity status was as the difference of skeletal age (SA, Fels method) minus CA. RESULTS: Fat-free mass was the most prominent single predictor of LVM (R2 = 36.6%). It was associated with an allometric coefficient close to linearity (k = 0.924, 95%CI: 0.737 to 1.112). A significant multiplicative allometric model including body mass, fat-free mass, CA, training experience and skeletal maturity status was also obtained (R = 0.684; R2 = 46.2%). CONCLUSION: Stature has limitations as a valid size descriptor of LVM. Body mass, fat-free mass, training experience, CA, body mass and skeletal maturity status were relevant factors contributing to inter-individual variability in LVM.

Allometric Modeling of Wingate Test among Adult Male Athletes from Combat Sports.

Background and objectives: Athletes from combat sports are grouped into a series of weight categories that are intended to promote fair competition. Differences in performance are partly attributable to differences in body size. Consequently, ratio standards in which a performance variable is simply divided by an anthropometric characteristic such as body mass are often used, although this application is not recommended. This study aimed to obtain allometric models to interpret Wingate Anaerobic Test (WAnT) outputs among male adult athletes from combat sports. Materials and Methods: The sample was composed of 64 participants aged 18-39 years (24.2 ± 4.6 years). Stature and body mass (BM) were measured and air displacement plethysmography used to estimate fat mass and fat-free mass (FFM). Lower-limb lean soft tissue (LL-LST) was derived from dual energy X-ray absorptiometry. WAnT outputs were peak power (WAnT-PP) and mean power (WAnT-MP). Allometric models were obtained from simple and multiple linear regressions using log-transformed variables. Results: Models derived from a single three-dimension descriptor explained a large portion of variance: WAnT-PP (BM: 31.1%; FFM: 54%; LL-LST: 47.2%) and WAnT-MP (BM: 50.1%; FFM: 57.4%; LL-LST: 62.7%). Finally, the best proportional allometric models emerged from the combination of LL-LST and FFM (WAnT-PP: 55%; WAnT-MP: 65%). Conclusions: The relationship between weight categories and performance did not seem to be explained by the basic principles of geometric similarity.

Allometric scaling of aerobic fitness outputs in school-aged pubertal girls.

BACKGROUND: This study aimed to determine the allometric exponents for concurrent size descriptors (stature, body mass and fat-free mass) and also to examine the contribution of chronological age and pubertal status combined with above mentioned size descriptors to explain inter-individual variability in the peak of oxygen uptake (VO2peak) among girls during circumpubertal years. METHODS: The final sample included 51 girls (10.7-13.5 years). VO2peak was derived from an incremental progressive maximal protocol using a motorized treadmill. Anthropometry included body mass, stature and skinfolds. Measurements were performed by a single trained observer. Sexual maturation was assessed as self-reported stage of pubic hair (PH) development. Static allometric models were explored as an alternative to physiological output per unit of size descriptors. Allometry also considered chronological age and sexual maturation as dummy variable (PH2 vs. PH3 and PH3 vs. PH4). RESULTS: Scaling coefficients for stature, body mass and fat-free mass were 1.463 (95%CI: 0.476 to 2.449), 0.516 (95%CI: 0.367 to 0.666) and 0.723 (95%CI: 0.494 to 0.951), respectively. The inclusion of sexual maturation increased explained variance for VO2peak (55% for PH2 vs. PH3 and 47% for PH3 vs. PH4). Body mass was identified as the most prominent body size descriptor in the PH2 vs. PH3 while fat-free mass was the most relevant predictor combined with PH3 vs. PH4. CONCLUSIONS: Body mass and fat-free mass seemed to establish a non-linear relationship with VO2peak. Across puberty, inter-individual variability in VO2peak is explained by sexual maturation combined with whole body during early puberty and by sexual maturation and fat-free mass during late puberty. Additional studies need to confirm ontogenetic allometric models during years of maximal growth.

Total and regional bone mineral and tissue composition in female adolescent athletes: comparison between volleyball players and swimmers.

BACKGROUND: Exploring the osteogenic effect of different bone-loading sports is particular relevant to understand the interaction between skeletal muscle and bone health during growth. This study aimed to compare total and regional bone and soft-tissue composition between female adolescent swimmers (n=20, 15.71±0.93 years) and volleyball players (n=26, 16.20±0.77 years). METHODS: Dietary intake was obtained using food frequency questionnaires. Body size was given by stature, sitting height, and body mass. Six skinfolds were measured. Bone mineral content (BMC) and density (BMD), lean soft tissue, and fat tissue were assessed using dual-energy X-ray absorptiometry. Pearson's product moment correlation coefficients were calculated to examine the relationships among variables, by type of sport. Comparisons between swimmers and volleyball players were performed using student t-tests for independent samples and multivariate analysis of covariance (controlling for age, training history and body size). RESULTS: Swimmers (BMC: 2328±338 g) and volleyball players (BMC: 2656±470 g) exceeded respectively by 2.1 and 2.8 standard deviation scores the average of international standards for whole body BMC of healthy adolescents. Years of training in swimmers were positively related to the upper limbs BMC (r=+0.49, p<0.05). In volleyball players, years of training correlated significantly with lower limbs BMD (r=+0.43, p<0.05). After adjustments for potential confounders, moderate differences (ES-r=0.32) between swimmers and volleyball players were noted in BMD at the lower limbs (volleyball players: +0.098 g∙cm-2, +7.8%). CONCLUSIONS: Youth female athletes who participate in high-intensity weight-loading activities such as volleyball exhibit moderately higher levels of BMD at the lower limbs compared to non-loading sports such as swimming.

Far from the Madding Crowd: the Molecular Basis for Immunological Escape of Plasmodium falciparum.

Like Thomas Hardy's famous novel Far from the Madding Crowd, Plasmodium falciparum parasites display their most relevant survival structures (proteins) involved in host cell invasion far away from the immune system's susceptible regions, displaying tremendous genetic variability, to attract the immune response and escape immune pressure. The 3D structure localisation of the conserved amino acid sequences of this deadly parasite's most relevant proteins involved in host cell invasion, as well as the location of the highly polymorphic, highly immunogenic regions, clearly demonstrates that such structures are far apart, sometimes 90° to 180° opposite, thereby rendering the immune response useless. It is also shown here that these conserved, functionally-relevant structures are immunologically silent, since no immune response has been induce.

Critical role of HLA-DRß* binding peptides' peripheral flanking residues in fully-protective malaria vaccine development.

A vaccine candidate component must fit perfectly into the antigen presenting HLA-DRß* molecule's groove (or canonical nonapeptide) peptide binding region (PBR) during antigen presentation to the T-cell receptor (TCR), conforming a specific and stable macromolecular complex and induce an appropriate immune response. Antigen's peripheral flanking residues (PFR, positions (p) -p2 and p10) must thus establish strong interactions with the HLA-DRß* - TCR complex. These amino acids (aa) have specific physico-chemical characteristics enabling differentiation between non-protective but antibody-inducer (NPAI), short-lived protection inducer (SLPI) and long-lasting protection inducer (LLPI) peptides when used as an antimalarial vaccine component. Their identification (through 1H-NMR and Aotus monkey immunization) and proper modification contributes to a logical and rational methodology for long-lasting and protective immunological memory.

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

More than 50 years ago the owl monkey (genus Aotus) was found to be highly susceptible to developing human malaria, making it an excellent experimental model for this disease. Microbes and parasites' (especially malaria) tremendous genetic variability became resolved during our malaria vaccine development, involving conserved peptides having high host cell binding activity (cHABPs); however, cHABPs are immunologically silent and must be specially modified (mHABPs) to induce a perfect fit into major histocompatibility complex (MHC) molecules (HLA in humans). Since malarial immunity is mainly antibody-mediated and controlled by the HLA-DRB genetic region, ∼1000 Aotus have been molecularly characterised for MHC-DRB, revealing striking similarity between human and Aotus MHC-DRB repertories. Such convergence suggested that a large group of immune protection-inducing protein structures (IMPIPS), highly immunogenic and protection inducers against malarial intravenous challenge in Aotus, could easily be used in humans for inducing full protection against malaria. We highlight the value of a logical and rational methodology for developing a vaccine in an appropriate animal model: Aotus monkeys.

Group VII Ethylene Response Factors Coordinate Oxygen and Nitric Oxide Signal Transduction and Stress Responses in Plants.

The group VII ethylene response factors (ERFVIIs) are plant-specific transcription factors that have emerged as important regulators of abiotic and biotic stress responses, in particular, low-oxygen stress. A defining feature of ERFVIIs is their conserved N-terminal domain, which renders them oxygen- and nitric oxide (NO)-dependent substrates of the N-end rule pathway of targeted proteolysis. In the presence of these gases, ERFVIIs are destabilized, whereas an absence of either permits their accumulation; ERFVIIs therefore coordinate plant homeostatic responses to oxygen availability and control a wide range of NO-mediated processes. ERFVIIs have a variety of context-specific protein and gene interaction partners, and also modulate gibberellin and abscisic acid signaling to regulate diverse developmental processes and stress responses. This update discusses recent advances in our understanding of ERFVII regulation and function, highlighting their role as central regulators of gaseous signal transduction at the interface of ethylene, oxygen, and NO signaling.

Effectiveness and safety of medication abortion via telemedicine versus in-person: A cohort of pregnant people in Colombia.

OBJECTIVE: To compare the effectiveness and safety of medication abortion (MAB) via telemedicine versus in-person in pregnant people with less than 12 gestational weeks in Colombia. STUDY DESIGN: A retrospective cohort study was conducted with 23,362 pregnant people who requested MAB service from Profamilia (a Colombian non-governmental organization) in 2021-2022. The outcomes were success and safety of MAB. We performed a descriptive and a multivariate statistical analysis using the binary regression model to obtain an adjusted Odds Ratio (aOR) to identify factors associated with abortion success. RESULTS: In comparison to in-person care (n = 20,289), individuals in telemedicine (n = 3073) were predominantly from urban areas, belonged to a lower socioeconomic stratum, single and did not identify with any ethnic group. In-person users tended to have higher levels of education and accessed the service through private insurance (p < 0,05). There were no differences in the odd of a successful abortion based on the modality of care (aOR 1.18; 95% CI=0.87-1.59). The results were also the same with sensitivity analysis stratified: pregnant people who were nine weeks gestation or less (aOR 0.86; 95% CI=0.63-1.17) or more (aOR 0.87; 95% CI=0.28-2.65). CONCLUSION: Telemedicine is an effective and safe option for MAB, as in-person care. Telemedicine has the potential to increase abortion access by extending the availability of providers and offering people a new option for obtaining care conveniently and privately, especially for women with disadvantaged socioeconomic and educational background. IMPLICATIONS: This study demonstrates that medication abortion (MAB) administered via telemedicine produces outcomes akin to those of in-person care, providing a compelling rationale for its adoption, particularly in underserved regions. This approach can be replicated in other countries in Latin America and the Caribbean.

Learning effect on an isokinetic knee strength test protocol among male adolescent athletes.

Learning effect occurs when the best performance is not achieved at the earliest trial of a repeated protocol of evaluation. The present study examined, within testing session, the intra-individual variation in an isokinetic strength protocol composed of five reciprocal concentric and eccentric contractions of knee extensors (KE) and knee flexors (KF) among male adolescent swimmers. Additionally, test-retest reliability was determined as intra-individual mean differences between two consecutive testing sessions. The sample included 38 swimmers aged 10.1-13.3 years. A subsample (n = 17) completed a second visit. Isokinetic dynamometry was used to assess concentric and eccentric contractions of KE and KF at an angular velocity of 60°.s-1. The protocol included three preliminary repetitions that were not retained for analysis, a 60-second interval, and five reciprocal maximal concentric contractions (cc). The preceding sequence was repeated for eccentric contractions (ecc) of KE and KF. Multilevel regression confirmed intra-individual and inter-individual levels as significant sources of variance in peak torque (PT) values. Intra-class correlation (ICC) fluctuated between 0.582 and 0.834 and, in general, a substantial percentage of participants need more than three repetitions to attain their best PT: KEcc (36.8%), KEecc (23.7%), KFcc (39.5%), KFecc (18.4%). For the subsample of 17 swimmers who completed a second testing session, intra-individual mean differences of the best PT were trivial or small. In summary, the validity of shorter protocols may be compromised if swimmers do not attain their best peak torque in the first few attempts, and the reliability of a 5-repetition protocol seemed acceptable.

Stereo electronic principles for selecting fully-protective, chemically-synthesised malaria vaccines.

Major histocompatibility class II molecule-peptide-T-cell receptor (MHCII-p-TCR) complex-mediated antigen presentation for a minimal subunit-based, multi-epitope, multistage, chemically-synthesised antimalarial vaccine is essential for inducing an appropriate immune response. Deep understanding of this MHCII-p-TCR complex's stereo-electronic characteristics is fundamental for vaccine development. This review encapsulates the main principles for achieving such epitopes' perfect fit into MHC-II human (HLADRß̞1*) or Aotus (Aona DR) molecules. The enormous relevance of several amino acids' physico-chemical characteristics is analysed in-depth, as is data regarding a 26.5 ± 2.5Å distance between the farthest atoms fitting into HLA-DRß1* structures' Pockets 1 to 9, the role of polyproline II-like (PPIIL) structures having their O and N backbone atoms orientated for establishing H-bonds with specific HLA-DRß1*-peptide binding region (PBR) residues. The importance of residues having specific charge and orientation towards the TCR for inducing appropriate immune activation, amino acids' role and that of structures interfering with PPIIL formation and other principles are demonstrated which have to be taken into account when designing immune, protection-inducing peptide structures (IMPIPS) against diseases scourging humankind, malaria being one of them.

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World's Population.

Fifty ~20-amino acid (aa)-long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus' main genetic variants for complementary trial C-21. Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.e., aa predilection for polyproline type II left-handed (PPIIL) formation, replacing ß-branched, aromatic aa, short-chain backbone H-bond-forming residues, π-π interactions (n→π* and π-CH), aa interaction with π systems, and molecular fragments able to interact with them, disrupting PPIIL propensity formation. All these modified structures had PPIIL formation propensity to enable target peptide interaction with human leukocyte antigen-DRß1* (HLA-DRß1*) molecules to mediate antigen presentation and induce an appropriate immune response. Such modified peptides were designed for human use; however, they induced high antibody titres against S, M, and E parental mutant peptides and neutralising antibodies when suitably modified and chemically synthesised for immunising 61 major histocompatibility complex class II (MHCII) DNA genotyped Aotus monkeys (matched with their corresponding HLA-DRß1* molecules), predicted to cover 77.5% to 83.1% of the world's population. Such chemically synthesised peptide mixture represents an extremely pure, stable, reliable, and cheap vaccine for COVID-19 pandemic control, providing a new approach for a logical, rational, and soundly established methodology for other vaccine development.

The First Chemically-Synthesised, Highly Immunogenic Anti-SARS-CoV-2 Peptides in DNA Genotyped Aotus Monkeys for Human Use.

Thirty-five peptides selected from functionally-relevant SARS-CoV-2 spike (S), membrane (M), and envelope (E) proteins were suitably modified for immunising MHC class II (MHCII) DNA-genotyped Aotus monkeys and matched with HLA-DRß1* molecules for use in humans. This was aimed at producing the first minimal subunit-based, chemically-synthesised, immunogenic molecules (COLSARSPROT) covering several HLA alleles. They were predicted to cover 48.25% of the world's population for 6 weeks (short-term) and 33.65% for 15 weeks (long-lasting) as they induced very high immunofluorescent antibody (IFA) and ELISA titres against S, M and E parental native peptides, SARS-CoV-2 neutralising antibodies and host cell infection. The same immunological methods that led to identifying new peptides for inclusion in the COLSARSPROT mixture were used for antigenicity studies. Peptides were analysed with serum samples from patients suffering mild or severe SARS-CoV-2 infection, thereby increasing chemically-synthesised peptides' potential coverage for the world populations up to 62.9%. These peptides' 3D structural analysis (by 1H-NMR acquired at 600 to 900 MHz) suggested structural-functional immunological association. This first multi-protein, multi-epitope, minimal subunit-based, chemically-synthesised, highly immunogenic peptide mixture highlights such chemical synthesis methodology's potential for rapidly obtaining very pure, highly reproducible, stable, cheap, easily-modifiable peptides for inducing immune protection against COVID-19, covering a substantial percentage of the human population.