Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination

Science Immunology, Journal Year: 2022, Volume and Issue: 7(76)

Published: July 19, 2022

SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether elicits effective immune responses respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared S-specific total neutralizing antibody responses, B T cell immunity, bronchoalveolar lavage fluid (BAL) blood COVID-19-vaccinated individuals hospitalized patients. Vaccinated had significantly lower levels D614G, Delta (B.1.617.2), Omicron BA.1.1 BAL with COVID-19 convalescents despite blood. Furthermore, induced circulating but contrast to convalescents, these were absent vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic alone weak mucosal especially mice; combination plus adenovirus-S strong not only ancestral virus also variant. Together, our study supports contention current vaccines are highly severe disease development, likely through recruiting during reinfection, offer limited protection breakthrough infection, by sublineage. Hence, booster needed establish sterilizing tract SARS-CoV-2, infection sublineage future VOCs.

Language: Английский

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Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(4), P. e248051 - e248051

Published: April 23, 2024

Importance There is still considerable controversy in the literature regarding capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response. Objective To compare serum and salivary IgG IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection. Design, Setting, Participants In this cohort study, SARS-CoV-2–naive participants those infection were consecutively included CoviCompare P M mRNA trials followed up day 180 after either BNT162b2 (Pfizer-BioNTech) vaccine mRNA-1273 (Moderna) at beginning COVID-19 campaign (from February 19 June 8, 2021) France. Data analyzed from October 25, 2022, July 13, 2023. Main Outcomes Measures An ultrasensitive digital enzyme-linked immunosorbent assay was used for comparison spike-specific levels. Spike-specific secretory level also quantified selected times. Results A total 427 3 groups: prior who received 1 single dose (n = 120) 2 doses 172) 135). The median age 68 (IQR, 39-75) years, 228 (53.4%) men. saliva increased injections individuals. After vaccination, SARS-CoV-2–specific levels, normalized respect significantly higher infection, as compared most responsive recipients (median 155 × 10 −5 vs 37 29; 107 54 57; 104 70 [ < .001]). contrast, 1, BNT162b2-vaccinated group only 57 (36 49 .01]). Bona fide multimeric antigenic stimulations optical density, 0.36 [IQR, 0.16-0.63] 0.16 0.10-0.22]; .001). Conclusions Relevance findings study suggest that associated immunity but much lower than previously infected Further studies are needed determine association between specific prevention transmission.

Language: Английский

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Microglia in retinal angiogenesis and diabetic retinopathy

Angiogenesis, Journal Year: 2024, Volume and Issue: 27(3), P. 311 - 331

Published: April 2, 2024

Abstract Diabetic retinopathy has a high probability of causing visual impairment or blindness throughout the disease progression and is characterized by growth new blood vessels in retina at an advanced, proliferative stage. Microglia are resident immune population central nervous system, known to play crucial role regulating retinal angiogenesis both physiological pathological conditions, including diabetic retinopathy. Physiologically, they located close essential for forming (neovascularization). In retinopathy, microglia become widely activated, showing distinct polarization phenotype that leads their accumulation around neovascular tufts. These activated induce pathogenic through secretion various angiogenic factors status endothelial cells. Interestingly, some subtypes simultaneously promote regression neovascularization tufts normal lesions. Modulating state microglial activation ameliorate thus appears as promising potential therapeutic approach managing Graphical abstract

Language: Английский

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SARS-CoV-2 XBB.1.5 mRNA booster vaccination elicits limited mucosal immunity

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(770)

Published: Oct. 23, 2024

Current COVID-19 vaccines provide robust protection against severe disease but minimal acquisition of infection. Intramuscularly administered induce serum neutralizing antibodies (NAbs), their ability to boost mucosal immune responses remains be determined. In this study, we show that the XBB.1.5 messenger RNA (mRNA) boosters result in increased neutralization multiple acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants humans, including dominant circulating variant JN.1. contrast, found mRNA booster did not augment NAbs or IgA responses, although SARS-CoV-2 XBB infection substantially antibody responses. These data demonstrate current enhance peripheral do robustly increase Our highlight a separation between and systems humans emphasize importance developing next-generation immunity protect virus infections.

Language: Английский

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Antibody and B Cell Responses to SARS-CoV-2 Infection and Vaccination: The End of the Beginning

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2023, Volume and Issue: 19(1), P. 69 - 97

Published: Sept. 22, 2023

As the COVID-19 pandemic has evolved during past years, interactions between human immune systems, rapidly mutating and selected SARS-CoV-2 viral variants, effective vaccines have complicated landscape of individual immunological histories. Here, we review some key findings for antibody B cell-mediated immunity, including responses to highly mutated omicron variants; imprinting other impacts successive antigenic variant exposures on cell memory; in secondary lymphoid mucosal tissues non-neutralizing antibody-mediated immunity; populations vulnerable severe disease such as those with cancer, immunodeficiencies, comorbidities, well showing apparent resistance many African populations; evidence involvement postacute sequelae infection or long COVID. Despite initial phase ending, will continue face challenges presented by this unpredictable virus.

Language: Английский

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Therapeutic antibodies and alternative formats against SARS-CoV-2

Antiviral Research, Journal Year: 2024, Volume and Issue: 223, P. 105820 - 105820

Published: Feb. 1, 2024

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) heavily burdened the entire world. Despite a prompt generation of vaccines and therapeutics to confront infection, virus remains threat. ancestor viral strain has evolved into several variants concern, with Omicron variant now having many distinct sublineages. Consequently, most available antibodies targeting spike went obsolete thus new therapies or therapeutic formats are needed. In this review we focus on antibody targets, provide an overview progress made so far, describe novel being explored, lessons learned from that can enhance preparedness.

Language: Английский

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Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(1), P. e1012456 - e1012456

Published: Jan. 23, 2025

The continued evolution of SARS-CoV-2 variants capable subverting vaccine and infection-induced immunity suggests the advantage a broadly protective against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from recovered-vaccinated donors neutralizing many other β-CoVs. Many these mAbs target conserved S2 stem region spike protein, rather than receptor binding domain contained within S1 primarily targeted by current vaccines. One S2-directed mAbs, CC40.8, has demonstrated efficacy in small animal models challenge. As next step pre-clinical testing as strategy to protect infection, we evaluated vivo CC40.8 clinically relevant non-human primate model conducting passive antibody transfer rhesus macaques (RM) followed mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n = 6) RM, alongside one group that received control (PGT121). Viral loads lower airway were significantly reduced animals receiving higher doses CC40.8. We observed significant reduction inflammatory cytokines macrophages with 10mg/kg 1mg/kg genome sequencing lack escape mutations epitope. Collectively, data demonstrate efficiency S2-targeting infection while providing critical preclinical work necessary for development pan–β-CoV

Language: Английский

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Beyond the Pandemic Era: Recent Advances and Efficacy of SARS-CoV-2 Vaccines Against Emerging Variants of Concern

Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 424 - 424

Published: April 17, 2025

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating severity clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have developed to this effect, including BioNTech-Pfizer Moderna’s mRNA vaccines, as well adenovirus vector-based such Oxford–AstraZeneca. However, emergence new variants subvariants SARS-CoV-2, characterized by enhanced transmissibility immune evasion, poses significant challenges efficacy current vaccination strategies. In review, we aim comprehensively outline landscape emerging concern (VOCs) sub-lineages that recently surfaced post-pandemic years. We assess effectiveness existing their booster doses, against these subvariants, BA.2-derived sub-lineages, XBB BA.2.86 (Pirola). Furthermore, discuss latest advancements vaccine technology, multivalent pan-coronavirus approaches, along development several next-generation coronavirus exosome-based, virus-like particle (VLP), mucosal, nanomaterial-based vaccines. Finally, highlight key critical areas for future research address evolving threat develop strategies combating viral threats, thereby improving preparedness pandemics.

Language: Английский

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Transfer of SARS-CoV-2 nucleocapsid protein to uninfected epithelial cells induces antibody-mediated complement deposition

Cell Reports, Journal Year: 2025, Volume and Issue: 44(5), P. 115512 - 115512

Published: May 1, 2025

Language: Английский

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Intramuscular vaccination against SARS-CoV-2 transiently induces neutralizing IgG rather than IgA in the saliva

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 5, 2024

The mucosal immunity is crucial for restricting SARS-CoV-2 at its entry site. Intramuscularly applied vaccines against stimulate high levels of neutralizing Abs in serum, but the impact these intramuscular vaccinations on features less clear. Here, we analyzed kinetic and functional properties anti-SARS-CoV-2 saliva after vaccination with BNT162b2. We a total 24 healthy donors longitudinally up to 16 months. found that specific IgG appeared second vaccination, declined thereafter reappeared third vaccination. Adjusting serum same concentration revealed strong correlation between reactivity two compartments. Reactivity VoCs correlated strongly as seen by ELISAs RBD variants live-virus assays replication-competent viruses. For further analysis, purified IgA from saliva. In vaccinated activity towards authentic virus IgG, not fraction contrast, only breakthrough infection. both fractions. Together, show mRNA transiently induces mediated thus differs Waning might be linked susceptibility

Language: Английский

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