Towards the development of an epitope-focused vaccine for SARS-CoV-2

Cervantes‐Torres, Jacquelynne; Rosales, Sergio Gómez; Cabello, Carlos; Montero, Laura; Hernandez-Aceves, Juan; Granados, Guillermo; Calderón-Gallegos, Arturo; Zuñiga-Flores, Francisco J; Ruiz-Rivera, Mirna B.; Abarca-Magaña, Julio César; Ortega‐Francisco, Sandra; Olguín‐Alor, Roxana; Díaz, Georgina; Paczka-Garcia, Filipo; Zavala-Gaytan, Rubí; Vázquez‐Ramírez, Ricardo; Ayón-Nuñez, Dolores Adriana; Carrero, Julio César; Ríos-Valencia, Diana G.; Jasso-Ramírez, Mariana; Vázquez-Hernández, Rebeca; Venegas, David; Garzón, Daniel; Cobos-Marín, Laura; Segura‐Velázquez, René; Villalobos, Nelly; Meneses, Gabriela; Zúñiga, Joaquı́n; Gamba, Gerardo; Cárdenas, Graciela; Hernández, Marisela; Parkhouse, Michael; Romano, Marta; Ruiz, Raúl José Bobes; Pérez-Tapia, Mayra; Huerta, Leonor; Fierro, Nora A.; Gràcia, I.; Soldevilla, Gloria; Fragoso, Gladis; Suárez-Güemes, Francisco; Laclette, Juan Pedro; Sciutto, Edda

doi:10.1016/j.vaccine.2022.09.059

Cited by 4 publications

(4 citation statements)

References 33 publications

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“…Despite the several vaccines produced, there is still a need for more effective and safe vaccines against COVID-19 as the causing virus, SARS-CoV-2, continues to spread worldwide (33). It is true for a number of vaccines that it was successful in developing a vaccine in record time, yet many challenges remain to be solved to overcome the COVID-19 pandemic emergency (11,34).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, other than DNA and mRNA vaccines, subunit (peptide) vaccines guarantee to preserve the required conformation and its final concentration (28)(29)(30)(31). Four used antigen polypeptides were selected by the structure and immunogenicity of spike protein (16,(32)(33)(34). In addition, polypeptide vaccines are easier and cheaper to manufacture on a large scale than mRNA vaccines and do not need ultra-cold storage.…”

Section: Introductionmentioning

confidence: 99%

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COVID-19 spike polypeptide vaccine reduces the pathogenesis and viral infection in a mouse model of SARS-CoV-2

Hisham

Seo²,

Kim³

et al. 2023

Front. Immunol.

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The SARS-CoV-2 coronavirus, which causes a respiratory disease called COVID-19, has been declared a pandemic by the World Health Organization (WHO) and is still ongoing. Vaccination is the most important strategy to end the pandemic. Several vaccines have been approved, as evidenced by the ongoing global pandemic, but the pandemic is far from over and no fully effective vaccine is yet available. One of the most critical steps in vaccine development is the selection of appropriate antigens and their proper introduction into the immune system. Therefore, in this study, we developed and evaluated two proposed vaccines composed of single and multiple SARS-CoV-2 polypeptides derived from the spike protein, namely, vaccine A and vaccine B, respectively. The polypeptides were validated by the sera of COVID-19-vaccinated individuals and/or naturally infected COVID-19 patients to shortlist the starting pool of antigens followed by in vivo vaccination to hACE2 transgenic mice. The spike multiple polypeptide vaccine (vaccine B) was more potent to reduce the pathogenesis of organs, resulting in higher protection against the SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

COVID-19 spike polypeptide vaccine reduces the pathogenesis and viral infection in a mouse model of SARS-CoV-2

Hisham

Seo²,

Kim³

et al. 2023

Front. Immunol.

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“…Sequence logos were used to assess the conservation of individual amino acids in each identified epitope, with the height of each letter indicating the proportion of sequences that contain the residue at that site (Figure 6). The majority of residues in 25 YVYYYQSAFRPPNGWHLQGGAYAVVNSTN 54 (Epitope 1) were shared amongst IBV serotypes QX, 4/91 and M41, but there were amino acid substitutions at positions 25,37,38,43,50, and 51-54 (Figure 6a). The epitope denoted as 83 AMTVPPAGMSWSVS 96 (Epitope 3) was also shared amongst serotypes, with some degree of variation evident in residues and where substitutions occurred (positions 85, 86, 88, 89, 92, and 95); there were changes in amino acid hydrophobicity when serine was in these positions (Figure 6c).…”

Section: Conservancy Of Selected Epitope Candidates Amongst Ibv Serot...mentioning

confidence: 99%

“…Several studies have identified neutralising epitopes present on the S glycoprotein of other coronaviruses, including severe acute respiratory syndrome (SARS) coronavirus (CoV) [35,36], SARS-CoV-2 [37][38][39], Middle East respiratory syndrome (MERS) CoV [40], mouse hepatitis virus (MHV) [41], porcine epidemic diarrhea virus (PEDV) [42], and transmissible gastroenteritis virus (TGEV) [43], through a variety of epitope-mapping approaches including computational structural analysis of receptor binding sites, in silico predictions, and phage display. Many protective and neutralising epitopes tend to be conformational in nature, and B-cell epitopes are often discontinuous with a characteristic residue length of 5-20 amino acids, with a shorter peptide spanning most of the epitope's key functional residues [44].…”

Section: Introductionmentioning

confidence: 99%

Revealing Novel-Strain-Specific and Shared Epitopes of Infectious Bronchitis Virus Spike Glycoprotein Using Chemical Linkage of Peptides onto Scaffolds Precision Epitope Mapping

Sives,

Keep,

Bickerton

et al. 2023

Viruses

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The avian coronavirus, infectious bronchitis virus (IBV), is an economically important infectious disease affecting chickens, with a diverse range of serotypes found globally. The major surface protein, spike (S), has high diversity between serotypes, and amino acid differences in the S1 sub-unit are thought to be responsible for poor cross-protection afforded by vaccination. Here, we attempt to address this, by using epitope mapping technology to identify shared and serotype-specific immunogenic epitopes of the S glycoprotein of three major circulating strains of IBV, M41, QX, and 4/91, via CLIPS peptide arrays based on peptides from the S1 sub-units. The arrays were screened with sera from chickens immunised with recombinant IBV, based on Beau-R backbone expressing heterologous S, generated in two independent vaccination/challenge trials. The screening of sera from rIBV vaccination experiments led to the identification of 52 immunogenic epitopes on the S1 of M41, QX, and 4/91. The epitopes were assigned into six overlapping epitope binding regions. Based on accessibility and location in the hypervariable regions of S, three sequences, 25YVYYYQSAFRPPNGWHLQGGAYAVVNSTN54, 67TVGVIKDVYNQSVASI82, and 83AMTVPPAGMSWSVS96, were selected for further investigation, and synthetic peptide mimics were recognised by polyclonal sera. These epitopes may have the potential to contribute towards a broader cross-protective IBV vaccine.

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Caveats of chimpanzee ChAdOx1 adenovirus-vectored vaccines to boost anti-SARS-CoV-2 protective immunity in mice

Cervantes-Torres,

Cabello-Gutiérrez,

Ayón-Núñez

et al. 2024

Appl Microbiol Biotechnol

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Several COVID-19 vaccines use adenovirus vectors to deliver the SARS-CoV-2 spike (S) protein. Immunization with these vaccines promotes immunity against the S protein, but against also the adenovirus itself. This could interfere with the entry of the vaccine into the cell, reducing its efficacy. Herein, we evaluate the efficiency of an adenovirus-vectored vaccine (chimpanzee ChAdOx1 adenovirus, AZD1222) in boosting the specific immunity compared to that induced by a recombinant receptor-binding domain (RBD)-based vaccine without viral vector. Mice immunized with the AZD1222 human vaccine were given a booster 6 months later, with either the homologous vaccine or a recombinant vaccine based on RBD of the delta variant, which was prevalent at the start of this study. A significant increase in anti-RBD antibody levels was observed in rRBD-boosted mice (31–61%) compared to those receiving two doses of AZD1222 (0%). Significantly higher rates of PepMix™- or RBD-elicited proliferation were also observed in IFNγ-producing CD4 and CD8 cells from mice boosted with one or two doses of RBD, respectively. The lower efficiency of the ChAdOx1-S vaccine in boosting specific immunity could be the result of a pre-existing anti-vector immunity, induced by increased levels of anti-adenovirus antibodies found both in mice and humans. Taken together, these results point to the importance of avoiding the recurrent use of the same adenovirus vector in individuals with immunity and memory against them. It also illustrates the disadvantages of ChAdOx1 adenovirus-vectored vaccine with respect to recombinant protein vaccines, which can be used without restriction in vaccine-booster programs. Key points • ChAdOx1 adenovirus vaccine (AZD1222) may not be effective in boosting anti-SARS-CoV-2 immunity • A recombinant RBD protein vaccine is effective in boosting anti-SARS-CoV-2 immunity in mice • Antibodies elicited by the rRBD-delta vaccine persisted for up to 3 months in mice

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Towards the development of an epitope-focused vaccine for SARS-CoV-2

Cited by 4 publications

References 33 publications

COVID-19 spike polypeptide vaccine reduces the pathogenesis and viral infection in a mouse model of SARS-CoV-2

COVID-19 spike polypeptide vaccine reduces the pathogenesis and viral infection in a mouse model of SARS-CoV-2

Revealing Novel-Strain-Specific and Shared Epitopes of Infectious Bronchitis Virus Spike Glycoprotein Using Chemical Linkage of Peptides onto Scaffolds Precision Epitope Mapping

Caveats of chimpanzee ChAdOx1 adenovirus-vectored vaccines to boost anti-SARS-CoV-2 protective immunity in mice

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