Trimeric protein vaccine based on Beta variant elicits robust immune response against BA.4/5-included SARS-CoV-2 Omicron variants

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: March 10, 2023

Abstract The current Coronavirus Disease 2019 (COVID-19) pandemic, induced by newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants, posed great threats to global public health security. There is an urgent need design effective next‑generation vaccines against lineages. Here, we investigated the immunogenic capacity of vaccine candidate based on receptor binding domain (RBD). An RBD β -HR self-assembled trimer including Beta variant (containing K417, E484 and N501) heptad repeat (HR) subunits was developed using insect cell expression platform. Sera obtained from immunized mice effectively blocked RBD-human angiotensin-converting enzyme (hACE2) for different viral showing robust inhibitory activity. In addition, -HR/trimer durably exhibited high titers specific antibodies levels cross-protective neutralizing lineages, as well other major variants Alpha, Beta, Delta. Consistently, also promoted a broad potent cellular immune response involving participation T follicular helper (Tfh) cells, germinal center (GC) B activated effector memory central which are critical facets protective immunity. These results demonstrated that candidates provided attractive next-generation strategy in effort halt spread SARS-CoV-2.

Language: Английский

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LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters

Viruses, Journal Year: 2023, Volume and Issue: 15(7), P. 1409 - 1409

Published: June 21, 2023

The SARS-CoV-2 pandemic demonstrated the need for potent and broad-spectrum vaccines. This study reports development testing of a lumpy skin disease virus (LSDV)-vectored vaccine against SARS-CoV-2, utilizing stabilized spike conserved nucleocapsid proteins as antigens to develop robust immunogenicity. Construction (LSDV-SARS2-S,N) was confirmed by polymerase chain reaction (PCR) amplification sequencing. In vitro characterization that cells infected with LSDV-SARS2-S,N expressed protein. BALB/c mice, elicited high magnitude IFN-γ ELISpot responses (spike: 2808 SFU/106 splenocytes) neutralizing antibodies (ID50 = 6552). Testing in hamsters, which emulate human COVID-19 progression, showed titers Wuhan Delta variants (Wuhan ID50 2905; 4648). Additionally, hamsters vaccinated displayed significantly less weight loss, lung damage, reduced viral RNA copies following infection variant compared controls, demonstrating protection disease. These data demonstrate LSDV-vectored vaccines display promise an effective potential platform communicable diseases humans animals. Further efficacy immune response analysis, particularly non-human primates, are warranted.

Language: Английский

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Vaccine Based on Recombinant Fusion Protein Combining HBV PreS with SARS-CoV-2 Wild-Type- and Omicron-Derived RBD Strongly Induces Omicron-Neutralizing Antibodies

Published: Jan. 16, 2024

Background: COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a recurrent endemic disease affecting whole world. Since November 2021, Omicron and its subvariants are dominating. In order to prevent courses of disease, vaccines needed boost maintain antibody levels capable neutralizing Omicron. Recently we produced characterized SARS-CoV-2 vaccine based on recombinant fusion protein consisting hepatitis B virus (HBV)-derived PreS two wild-type RBDs. Objectives: To develop PreS-RBD which induces high Omicron-specific antibodies. Methods: We designed, produced, compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix W-PreS-W O-PreS-O) chimeric (i.e., W-PreS-O) subunit vaccines. Immunogens were in vitro chemical methods, mass-spectrometry, circular dichroism combination with thermal denaturation immunological methods. addition, BALB/c mice immunized aluminum hydroxide-adsorbed proteins hydroxide alone placebo) study specific cytokine responses, safety neutralization. Results: Defined pure immunogens could be large amounts as secreted folded mammalian cells. Antibodies induced after vaccination different doses strain-specific, reacted RBD dose-dependent manner resulted mixed Th1/Th2 immune response. Interestingly, RBD-specific IgG comparable but W-PreS-O-induced neutralization titers against (median VNT50: 5000) 7- 2-fold higher than W-PreS-W- O-PreS-O-specific ones, respectively 6-fold those vaccine. Conclusion: Among tested immunogens, vaccine, W-PreS-O, highest Thus, W-PreS-O seems highly promising candidate for further preclinical clinical evaluation.

Language: Английский

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Lack of Induction of RBD-Specific Neutralizing Antibodies despite Repeated Heterologous SARS-CoV-2 Vaccination Leading to Seroconversion and Establishment of T Cell-Specific Memory in a Patient in Remission of Multiple Myeloma

Vaccines, Journal Year: 2022, Volume and Issue: 10(3), P. 374 - 374

Published: Feb. 27, 2022

Prophylactic vaccination against infectious diseases may induce a state of long-term protection in the otherwise healthy host. However, situation is less predictable immunocompromised patients and require adjustment schedules and/or basic therapy.A patient full remission multiple myeloma since last three years on maintenance therapy with pomalidomide, drug inhibiting angiogenesis cell growth, was vaccinated twice Comirnaty followed by two vaccinations Vaxzevria. Seroconversion SARS-CoV-2-specific cellular responses were monitored.No signs seroconversion or T memory observed after first "full immunization" Comirnaty. Consequently, long-term-maintenance Pomalidomide stopped additional shots Vaxzevria administered which seroconverted Spike(S)-protein specific antibody levels reaching 49 BAU/mL, mild S-peptide pool-specific proliferation, effector cytokine production (IL-2, IL-13), activation increased numbers CD3+CD4+CD25+ cells as compared to non-vaccinated control subjects. despite suspension immunosuppression administration total four consecutive heterologous SARS-CoV-2 vaccine shots, did not develop neutralizing RBD-specific antibodies.Despite immunomonitoring-based success, clear correlates protection, development antibodies could be achieved current vaccines. Thus, our report emphasizes need for improved active passive immunization strategies infections.

Language: Английский

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Serum Neutralization Against SARS-CoV-2 Variants Is Heterogenic and Depends on Vaccination Regimen

The Journal of Infectious Diseases, Journal Year: 2022, Volume and Issue: 227(4), P. 528 - 532

Published: Oct. 31, 2022

Omicron variants are still the dominant SARS-CoV-2 viruses worldwide, therefore determination of level protection from infection and severe disease is essential. Here, we investigated humoral cellular immunity individuals immunized by ChAdOx1, BNT162b2, mRNA-1273 our results show that IgG neutralization titers wane over time. However, strongest against BA.1 T-cell responses were detected in ChAdOx1 vaccinees 6 months after second dose, while no long-lasting was shown BA.2 any cohort. Crucially, investigation revealed concern heterogenic dependent on immunization status.

Language: Английский

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Dissection of Antibody Responses of Gam-COVID-Vac-Vaccinated Subjects Suggests Involvement of Epitopes Outside RBD in SARS-CoV-2 Neutralization

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5104 - 5104

Published: March 7, 2023

Millions of people have been vaccinated with Gam-COVID-Vac but fine specificities induced antibodies not fully studied. Plasma from 12 naïve and 10 coronavirus disease 2019 (COVID-19) convalescent subjects was obtained before after two immunizations Gam-COVID-Vac. Antibody reactivity in the plasma samples (n = 44) studied on a panel micro-arrayed recombinant folded unfolded severe acute respiratory syndrome 2 (SARS-CoV-2) proteins 46 peptides spanning spike protein (S) by immunoglobulin G (IgG) subclass enzyme-linked immunosorbent assay (ELISA). The ability Gam-COVID-Vac-induced to inhibit binding receptor-binding domain (RBD) its receptor angiotensin converting enzyme (ACE2) investigated molecular interaction (MIA). virus-neutralizing capacity pseudo-typed virus neutralization test (pVNT) for Wuhan-Hu-1 Omicron. We found that vaccination significant increases IgG1 other IgG subclasses against S, subunit 1 (S1), (S2), RBD comparable manner subjects. Virus highly correlated vaccination-induced specific novel peptide (i.e., 12). Peptide located close N-terminal part S1 may potentially be involved transition pre- post-fusion conformation protein. In summary, S-specific naive manner. Besides RBD, N-terminus were also associated virus-neutralization.

Language: Английский

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Results of clinical trials phases I and II of MIR 19®

Immunologiya, Journal Year: 2023, Volume and Issue: 44(3), P. 291 - 316

Published: Jan. 1, 2023

Результаты I и II фазы клинических исследований препарата МИР 19 ® 1 Федеральное государственное бюджетное учреждение «Государственный научный центр «Институт иммунологии» Федерального медико-биологического агентства, 115522, г.Москва, Российская Федерация 2 автономное образовательное высшего образования «Российский национальный исследовательский медицинский университет имени Н.И.Пирогова» Министерства здравоохранения Российской Федерации, 117997, 3 научное «Научно-исследовательский институт вакцин сывороток им.И.И.Мечникова» науки 105064, 4 «Первый Московский государственный И.М

Language: Русский

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Vaccination with a bacterial peptide conjugated to SARS-CoV-2 receptor-binding domain accelerates immunity and protects against COVID-19

iScience, Journal Year: 2022, Volume and Issue: 25(8), P. 104719 - 104719

Published: July 5, 2022

Poor immunogenicity of critical epitopes can hamper vaccine efficacy. To boost immune recognition non- or low-immunogenic antigens, we developed a platform based on the conjugation target protein to chimeric designer peptide (CDP) bacterial origin. Here, exploited this Boost (iBoost) technology enhance response against receptor-binding domain (RBD) SARS-CoV-2 spike glycoprotein. Despite its fundamental role during viral infection, RBD is only moderately immunogenic. Immunization studies in mice showed that CDP induced superior responses compared alone. CDP-RBD elicited cross-reactive antibodies variants concern Delta and Omicron. Furthermore, hamsters vaccinated with potent neutralizing antibody were fully protected from lung lesion formation upon challenge SARS-CoV-2. In sum, show iBoost conjugate provides valuable tool for both quantitatively qualitatively enhancing anti-viral immunity.

Language: Английский

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Flow Cytometry-Based Measurement of Antibodies Specific for Cell Surface-Expressed Folded SARS-CoV-2 Receptor-Binding Domains

Vaccines, Journal Year: 2024, Volume and Issue: 12(4), P. 377 - 377

Published: April 1, 2024

Background: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now become endemic and is currently one of the important virus infections regularly affecting mankind. The assessment immunity against SARS-CoV-2 its variants for guiding active passive immunization SARS-CoV-2-specific treatment strategies. Methods: We here devised a novel flow cytometry-based diagnostic platform cell-bound antigens. This based on collection HEK-293T cell lines which, as exemplified in our study, stably express receptor-binding domains (RBDs) S-proteins eight major variants, ranging from Wuhan-Hu-1 to Omicron. Results: RBD-expressing display comparable levels RBD surface cells, shown with anti-FLAG-tag antibodies directed N-terminally introduced 3x-FLAG sequence while functionality was proven ACE2 binding. exemplify usefulness specificity cell-based test direct binding IgG IgA SARS-CoV-2-exposed and/or vaccinated individuals which assay shows wide linear performance range both at very low high serum antibody concentrations. In another application, i.e., adsorption studies, proved be powerful tool measuring ratios individual variant-specific antibodies. Conclusion: have established toolbox antigens, may considered an addition armamentarium tests, allowing flexible quick adaptation new concern.

Language: Английский

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Mutational pressure drives enhanced release of proteasome-generated public CD8+ T cell epitopes from SARS-CoV-2 RBD of Omicron and its current lineages

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 3, 2024

SUMMARY The COVID-19 pandemic was the most dramatic in newest history with nearly 7 million deaths and global impact on mankind. Here we report binding index of 305 HLA class I molecules from 18,771 unique haplotypes 28,104 individuals to 821 peptides experimentally observed spike protein RBD 5 main SARS-CoV-2 strains hydrolyzed by human proteasomes constitutive immune catalytic phenotypes. Our data read that mutations hACE2-binding region 496-513 Omicron B.1.1.529 strain results a increase proteasome-mediated release two public epitopes. Global population analysis haplotypes, specific these peptides, demonstrated decreased mortality populations enriched after but not before December, 2021, when became dominant strain. Noteworthy, currently circulating BA.2.86 JN.1 lineages contain no amino acid substitutions thus preserving identified core

Language: Английский

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