COVID-19 mRNA vaccine protects against SARS-CoV-2 Omicron BA.1 infection in diet-induced obese mice through boosting host innate antiviral responses

EBioMedicine, Год журнала: 2023, Номер 89, С. 104485 - 104485

Опубликована: Фев. 27, 2023

Язык: Английский

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Omicron‐induced interferon signaling prevents influenza A H1N1 and H5N1 virus infection

Journal of Medical Virology, Год журнала: 2023, Номер 95(3)

Опубликована: Март 1, 2023

Recent findings in permanent cell lines suggested that SARS-CoV-2 Omicron BA.1 induces a stronger interferon response than Delta. Here, we show and BA.5 but not Delta induce an antiviral state air-liquid interface cultures of primary human bronchial epithelial cells monocytes. Both subvariants caused the production biologically active types I (α/β) III (λ) interferons protected from super-infection with influenza A viruses. Notably, abortive infection monocytes was sufficient to protect virus infection. Interestingly, while influenza-like illnesses surged during wave England, their spread rapidly declined upon emergence Omicron. Mechanistically, Omicron-induced signaling mediated via double-stranded RNA recognition by MDA5, as MDA5 knockout prevented it. The JAK/STAT inhibitor baricitinib inhibited Omicron-mediated response, suggesting it is MDA5-mediated production, which activates receptors then trigger signaling. In conclusion, our study (1) demonstrates only substantial physiologically relevant models, (2) shows protects super-infection, (3) indicates comparable states.

Язык: Английский

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Ability of SpikoGen®, an Advax‐CpG adjuvanted recombinant spike protein vaccine, to induce cross‐neutralising antibodies against SARS‐CoV‐2 variants

Immunology, Год журнала: 2023, Номер 170(2), С. 193 - 201

Опубликована: Май 18, 2023

Abstract SpikoGen® vaccine is a subunit COVID‐19 expressed in insect cells comprising recombinant spike protein extracellular domain formulated with Advax‐CpG55.2™ adjuvant. A Phase 2 trial was conducted 400 adult participants randomised 3:1 to receive two intramuscular doses of or saline placebo 3 weeks apart. Some later enrolled separate booster study and received third dose vaccine. This stored serum used assess the ability induce cross‐neutralising antibodies against SARS‐CoV‐2 variants concern. Sera taken at baseline after second from seronegative subjects evaluated using panel pseudotype lentivirus neutralisation assays for cross‐neutralise wide range variants, including Omicron BA.1, BA.2 BA.4/5. Stored samples who participated both 2‐dose 6 months were also analysed changes over time dose. Two dose, sera broadly cross‐neutralised most concern, albeit titres being ~10‐fold lower. While fell low levels subjects, they showed ~20‐fold rise booster, which there only ~2‐3‐fold difference ancestral strains. Despite based on Wuhan sequence, doses, induced antibodies. Titres then reduced but rapidly restored by booster. resulted high variants. data supports ongoing use protection recent

Язык: Английский

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SARS-CoV-2 Omicron Specific Mutations Affecting Infectivity, Fusogenicity, and Partial TMPRSS2-Independency

Viruses, Год журнала: 2023, Номер 15(5), С. 1129 - 1129

Опубликована: Май 9, 2023

The COVID-19 pandemic resulted from the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its first appearance in 2019, new SARS-CoV-2 variants concern (VOCs) have emerged frequently, changing infection’s dynamic. infects cells via two distinct entry routes; receptor-mediated endocytosis or membrane fusion, depending on absence presence transmembrane serine protease (TMPRSS2), respectively. In laboratory conditions, Omicron strain inefficiently predominantly and is phenotypically characterized by decreased syncytia formation compared to earlier Delta variant. Thus, it important characterize Omicron’s unique mutations their phenotypic manifestations. Here, utilizing pseudovirions, we report that specific Spike F375 residue decreases infectivity, conversion S375 sequence significantly increases infectivity. Further, identified Y655 TMPRSS2 dependency fusion. Y655H, K764N, K856N K969N revertant mutations, bearing variant sequence, increased cytopathic effect cell–cell suggesting these Omicron-specific residues reduced severity SARS-CoV-2. This study correlation mutational profile with outcome should sensitize our alertness towards emerging VOCs.

Язык: Английский

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Divergent trajectory of replication and intrinsic pathogenicity of SARS-CoV-2 Omicron post-BA.2/5 subvariants in the upper and lower respiratory tract

EBioMedicine, Год журнала: 2023, Номер 99, С. 104916 - 104916

Опубликована: Дек. 15, 2023

Earlier Omicron subvariants including BA.1, BA.2, and BA.5 emerged in waves, with a subvariant replacing the previous one every few months. More recently, post-BA.2/5 have acquired convergent substitutions spike that facilitated their escape from humoral immunity gained ACE2 binding capacity. However, intrinsic pathogenicity replication fitness of evaluated are not fully understood.

Язык: Английский

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