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

Patarroyo, Manuel Elkín; Patarroyo, Manuel A.; Alba, Martha Patricia; Pabón, Laura; Rugeles, Marı́a Teresa; Aguilar-Jiménez, Wbeimar; Florez, Lizdany; Bermúdez, Adriana; Rout, Ashok K.; Griesinger, Christian; Suárez, Carlos F.; Aza-Conde, Jorge; Reyes, César; Avendaño, Catalina; Samacá, Jhoan; Camargo, Anny; Silva, Yolanda; Forero, Martha; González, Edgardo

doi:10.3389/fimmu.2021.724060

Cited by 6 publications

(9 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD data collected at 27°C and 37°C provided striking results. Figure 9 indicates random coil peptides, similar to 1 H-NMR determination of highly protective, long-lived COLSARSPROT peptides ( 3 ). CD revealed that most (~85%) SM-COLSARSPROT peptides inducing high Ab titres (>0.3, 450-nm OD; Figures 8F, G ) targeting C-21 mixture native parental peptides had strong negative ellipticity at 190 nm (starting below 0 at 27°C and 37°C).…”

Section: Resultsmentioning

confidence: 56%

“…CD studies for ascertaining PPII L propensity involved 51/53 C-21 peptides due to the onerous task of 1 H-NMR 3D structure determination ( 3 ) for recognising modified SM-COLSARSPROT peptides’ secondary structure elements. CD data collected at 27°C and 37°C provided striking results.…”

Section: Resultsmentioning

confidence: 99%

“…The previously mentioned, upwardly orientated soluble side-chain rotamer orientation, volume, and charge ( 76 ) are also critical features for MHC–peptide–TCR complex formation; residues in p3 and p7 were replaced by aa having similar mass, surface, and volume by aliphatic or P aa (the latter preferred because P in these positions induced or increased PPII L propensity and T-cell activation) ( Figures 1B , C ) ( 3 , 77 , 78 ).…”

Section: Discussionmentioning

confidence: 97%

“…COLSARSPROT emerged from our fundamental, thoroughly analysed data, amassed over 35 years’ malaria vaccine research ( 4 , 5 ); physicochemical rules for modifying and making malaria high activity peptides (HAP) strongly immunogenic and protection ( 11 – 13 ) or neutralising antibody (NAb) inducers against SARS-CoV-2 infection led to the first multiprotein, multiepitope, minimal subunit-based, chemically synthesised, and highly immunogenic peptide mixture against SARS-CoV-2 ( 3 ). It was tested in MHCII DNA-genotyped Aotus monkeys for use in humans [great similarity (SI) and identity (ID) regarding human HLA-DR immune response genes and molecules] as antigen presentation by a host’s MHCII molecules for appropriate Ab production is the first/most critical step in immune activation.…”

Section: Introductionmentioning

confidence: 99%

“…Around 280 biologically derived vaccine candidates currently in development (some in phase IV clinical trials) are grouped by platform as being traditional (inactivated/live virus vaccines), recently licensed (recombinant protein/virus vectored) and/or never having been licensed (mRNA/DNA vaccines) ( 2 ); however, none are chemically synthesised. Data regarding the first synthetic peptide mixture, COLSARSPROT ( 3 ), have been published recently.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Patarroyo

Pabón

et al. 2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

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 β-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-DRβ1* (HLA-DRβ1*) 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-DRβ1* 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.

show abstract

Section: Resultsmentioning

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Patarroyo

Pabón

et al. 2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

Development and recent advancement in microfluidics for point of care biosensor applications: A review

Lakhera

Chaudhary

Bhardwaj

et al. 2022

Biosensors and Bioelectronics: X

View full text Add to dashboard Cite

Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic

Bach,

Ghanizada,

Kirkby

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: Antibodies play a key role in the immune defence against infectious pathogens. Understanding the underlying process of B cell recognition is not only of fundamental interest; it supports important applications within diagnostics and therapeutics. Whereas the nature of conformational B cell epitope recognition is inherently complicated, linear B cell epitopes offer a straightforward approach that potentially can be reduced to one of peptide recognition. Methods: Using an overlapping peptide approach representing the entire proteomes of the seven main coronaviruses known to infect humans, we analysed sera pooled from eight PCR-confirmed COVID-19 convalescents and eight pre-pandemic controls. Using a high-density peptide microarray platform, 13-mer peptides overlapping by 11 amino acids were in situ synthesised and incubated with the pooled primary serum samples, followed by development with secondary fluorochrome-labelled anti-IgG and -IgA antibodies. Interactions were detected by fluorescence detection. Strong Ig interactions encompassing consecutive peptides were considered to represent "high-fidelity regions" (HFRs). These were mapped to the coronavirus proteomes using a 60% homology threshold for clustering. Results: We identified 333 human coronavirus derived HFRs. Among these, 98 (29%) mapped to SARS-CoV-2, 144 (44%) mapped to one or more of the four circulating common cold coronaviruses (CCC), and 54 (16%) cross-mapped to both SARS-CoV-2 and CCCs. The remaining 37 (11%) mapped to either SARS-CoV or MERS-CoV. Notably, the COVID-19 serum was skewed towards recognising SARS-CoV-2-mapped HFRs, whereas the pre-pandemic was skewed towards recognising CCC-mapped HFRs. In terms of absolute numbers of linear B cell epitopes, the primary targets are the ORF1ab protein (60%), the spike protein (21%), and the nucleoprotein (15%) in that order; however, in terms of epitope density, the order would be reversed. Conclusion: We identified linear B cell epitopes across coronaviruses, highlighting pan-, alpha-, beta-, or SARS-CoV-2-corona-specific B cell recognition patterns. These findings could be pivotal in deciphering past and current exposures to epidemic and endemic coronavirus. Moreover, our results suggest that pre-pandemic anti-CCC antibodies may cross-react against SARS-CoV-2, which could explain the highly variable outcome of COVID-19. Finally, the methodology used here offers a rapid and comprehensive approach to high-resolution linear B-cell epitope mapping, which could be vital for future studies of emerging infectious diseases.

show abstract

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

Cited by 6 publications

References 88 publications

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

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

Development and recent advancement in microfluidics for point of care biosensor applications: A review

Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic

Contact Info

Product

Resources

About