Covalent coupling of Spike’s receptor binding domain to a multimeric carrier produces a high immune response against SARS-CoV-2

Berguer, Paula M.; Blaustein, Matı́as; Bredeston, Luis M.; Craig, Patricio O.; D’Alessio, Cecilia; Elias, Fernanda; Farré, Paola C.; Fernández, Natalia Brenda; Gentili, Hernán G.; Gándola, Yamila B.; Gasulla, Javier; Gudesblat, Gustavo E.; Herrera, María Georgina; Ibáñez, Lorena Itatí; Idrovo-Hidalgo, Tommy; Nadra, Alejandro D.; Noseda, Diego Gabriel; Paván, Carlos Humberto; Pavan, María F.; Pignataro, María Florencia; Román, Ernesto A.; Ruberto, Lucas; Rubinstein, Natalia; Sánchez, María Victoria; Santos, Javier; Wetzler, Diana E.; Zelada, Alicia M.

doi:10.1038/s41598-021-03675-0

Cited by 14 publications

(17 citation statements)

References 39 publications

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“…At present, vaccination is the most practical strategy for combating COVID-19. Most designed vaccines inhibit viral pathogenesis by targeting the S protein [ 12 , 13 ]. Hence, investigating the effect of the mutations is vital in determining the quality of vaccinations.…”

Section: Introductionmentioning

confidence: 99%

Mutations in SARS-CoV-2 structural proteins: a global analysis

Abavisani

Rahimian

Mahdavi

et al. 2022

Virol J

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Background Emergence of new variants mainly variants of concerns (VOC) is caused by mutations in main structural proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, we aimed to investigate the mutations among structural proteins of SARS-CoV-2 globally. Methods We analyzed samples of amino-acid sequences (AASs) for envelope (E), membrane (M), nucleocapsid (N), and spike (S) proteins from the declaration of the coronavirus 2019 (COVID-19) as pandemic to January 2022. The presence and location of mutations were then investigated by aligning the sequences to the reference sequence and categorizing them based on frequency and continent. Finally, the related human genes with the viral structural genes were discovered, and their interactions were reported. Results The results indicated that the most relative mutations among the E, M, N, and S AASs occurred in the regions of 7 to 14, 66 to 88, 164 to 205, and 508 to 635 AAs, respectively. The most frequent mutations in E, M, N, and S proteins were T9I, I82T, R203M/R203K, and D614G. D614G was the most frequent mutation in all six geographical areas. Following D614G, L18F, A222V, E484K, and N501Y, respectively, were ranked as the most frequent mutations in S protein globally. Besides, A-kinase Anchoring Protein 8 Like (AKAP8L) was shown as the linkage unit between M, E, and E cluster genes. Conclusion Screening the structural protein mutations can help scientists introduce better drug and vaccine development strategies.

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Section: Introductionmentioning

confidence: 99%

Mutations in SARS-CoV-2 structural proteins: a global analysis

Abavisani

Rahimian

Mahdavi

et al. 2022

Virol J

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“…Pseudovirus expressing Wuhan-Hu-1 SARS-CoV-2 S protein were produced by co-transfection of plasmids encoding a GFP protein (Addgene, 11619), a lentivirus backbone (VRC5602, NIH), and the S protein (VRC7475_2019-nCoV-S-WT, NIH) in HEK-293T cells as previously described [76]. To produce pseudoviruses expressing the S protein from different variants the following plasmids were used: Alpha (B.1.1.7) (InvivoGen, plv-spike-v2); Beta (B.1.351) (InvivoGEn, plv-spike-v3) and Delta (B.1.617.2) (InvivoGen, plv-spike-v8).…”

Section: Methodsmentioning

confidence: 99%

Nanobodies against SARS-CoV-2 reduced virus load in the brain of challenged mice and neutralized Wuhan, Delta and Omicron Variants

Pavan

Bok

Juan

et al. 2023

Preprint

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In this work, we developed llama-derived nanobodies (Nbs) directed to the receptor binding domain (RBD) and other domains of the Spike (S) protein of SARS-CoV-2. Nanobodies were selected after the biopanning of two Nb-libraries, one of which was generated after the immunization of a llama (lama glama) with the bovine coronavirus (BCoV) Mebus, and another with the full-length pre-fused locked S protein (S-2P) and the RBD from the SARS-CoV-2 Wuhan strain (WT). Most of the neutralizing Nbs selected with either RBD or S-2P from SARS-CoV-2 were directed to RBD and were able to block S2P/ACE2 interaction. Three Nbs recognized the N-terminal domain (NTD) of the S-2P protein as measured by competition with biliverdin, while some non-neutralizing Nbs recognize epitopes in the S2 domain. One Nb from the BCoV immune library was directed to RBD but was non-neutralizing. Intranasal administration of Nbs induced protection ranging from 40% to 80% against COVID-19 death in k18-hACE2 mice challenged with the WT strain. Interestingly, protection was not only associated with a significant reduction of virus replication in nasal turbinates and lungs, but also with a reduction of virus load in the brain. Employing pseudovirus neutralization assays, we were able to identify Nbs with neutralizing capacity against the Alpha, Beta, Delta and Omicron variants. Furthermore, cocktails of different Nbs performed better than individual Nbs to neutralize two Omicron variants (B.1.529 and BA.2). Altogether, the data suggest these Nbs can potentially be used as a cocktail for intranasal treatment to prevent or treat COVID-19 encephalitis, or modified for prophylactic administration to fight this disease.

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“…The neutralization activity of serum was determined by the decrease of GFP expression in infected HEK-293 T [ 32 ]. Briefly, SARS-CoV-2 S-pseudotyped lentivirus was produced by co-transfection of HEK-293 T cells with plasmids bearing the S protein, a lentivirus backbone (VRC5602, NIH) and a GFP reporter gene (Addgene plasmid #11,619).…”

Section: Methodsmentioning

confidence: 99%

COVID-19 Vaccination Responses with Different Vaccine Platforms in Patients with Inborn Errors of Immunity

et al. 2022

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Patients with inborn errors of immunity (IEI) in Argentina were encouraged to receive licensed Sputnik, AstraZeneca, Sinopharm, Moderna, and Pfizer vaccines, even though most of the data of humoral and cellular responses combination on available vaccines comes from trials conducted in healthy individuals. We aimed to evaluate the safety and immunogenicity of the different vaccines in IEI patients in Argentina. The study cohort included adults and pediatric IEI patients ( n = 118) and age-matched healthy controls (HC) ( n = 37). B cell response was evaluated by measuring IgG anti-spike/receptor binding domain (S/RBD) and anti-nucleocapsid(N) antibodies by ELISA. Neutralization antibodies were also assessed with an alpha-S protein-expressing pseudo-virus assay. The T cell response was analyzed by IFN-γ secretion on S- or N-stimulated PBMC by ELISPOT and the frequency of S-specific circulating T follicular-helper cells (TFH) was evaluated by flow cytometry. No moderate/severe vaccine-associated adverse events were observed. Anti-S/RBD titers showed significant differences in both pediatric and adult IEI patients versus the age-matched HC cohort ( p < 0.05). Neutralizing antibodies were also significantly lower in the patient cohort than in age-matched HC ( p < 0.01). Positive S-specific IFN-γ response was observed in 84.5% of IEI patients and 82.1% presented S-specific TFH cells. Moderna vaccines, which were mainly administered in the pediatric population, elicited a stronger humoral response in IEI patients, both in antibody titer and neutralization capacity, but the cellular immune response was similar between vaccine platforms. No difference in humoral response was observed between vaccinated patients with and without previous SARS-CoV-2 infection. In conclusion, COVID-19 vaccines showed safety in IEI patients and, although immunogenicity was lower than HC, they showed specific anti-S/RBD IgG, neutralizing antibody titers, and T cell-dependent cellular immunity with IFN-γ secreting cells. These findings may guide the recommendation for a vaccination with all the available vaccines in IEI patients to prevent COVID-19 disease. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-022-01382-7.

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Covalent coupling of Spike’s receptor binding domain to a multimeric carrier produces a high immune response against SARS-CoV-2

Cited by 14 publications

References 39 publications

Mutations in SARS-CoV-2 structural proteins: a global analysis

Mutations in SARS-CoV-2 structural proteins: a global analysis

Nanobodies against SARS-CoV-2 reduced virus load in the brain of challenged mice and neutralized Wuhan, Delta and Omicron Variants

COVID-19 Vaccination Responses with Different Vaccine Platforms in Patients with Inborn Errors of Immunity

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