Innate immune mechanisms of mRNA vaccines

Immunity, Journal Year: 2022, Volume and Issue: 55(11), P. 1993 - 2005

Published: Nov. 1, 2022

Language: Английский

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SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses

Immunity, Journal Year: 2023, Volume and Issue: 56(4), P. 879 - 892.e4

Published: March 22, 2023

Language: Английский

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Antibody-independent protection against heterologous SARS-CoV-2 challenge conferred by prior infection or vaccination

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(4), P. 633 - 643

Published: March 14, 2024

Abstract Vaccines have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity and mortality, yet emerging variants challenge their effectiveness. The prevailing approach to updating vaccines targets the antibody response, operating under presumption that it is primary defense mechanism following vaccination or infection. This perspective, however, can overlook role of T cells, particularly when levels are low absent. Here we show, through studies in mouse models lacking antibodies but maintaining functional B cells lymphoid organs, immunity conferred by prior infection mRNA protect against SARS-CoV-2 independently antibodies. Our findings, using three distinct inclusive a novel human/mouse ACE2 hybrid, highlight CD8 + essential for combating infections, whereas CD4 contribute managing milder cases, with interferon-γ having an important function this antibody-independent defense. These findings importance cell responses vaccine development, urging broader perspective on protective beyond just

Language: Английский

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Correlates of protection against symptomatic SARS-CoV-2 in vaccinated children

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(5), P. 1373 - 1383

Published: April 30, 2024

Abstract The paucity of information on longevity vaccine-induced immune responses and uncertainty the correlates protection hinder development evidence-based COVID-19 vaccination policies for new birth cohorts. Here, to address these knowledge gaps, we conducted a cohort study healthy 5–12-year-olds vaccinated with BNT162b2. We serially measured binding neutralizing antibody titers (nAbs), spike-specific memory B cell (MBC) spike-reactive T over 1 year. found that children mounted antibody, MBC after two doses BNT162b2, higher than adults 6 months vaccination. A booster (third) dose only improved without impacting responses. Among hybrid immunity, nAbs were highest in those infected vaccine doses. Binding IgG titers, predictive, cells being most important predictor against symptomatic infection before immunity; correlated immunity. stable time suggest sustained SARS-CoV-2 infection, even when wane. Booster vaccinations do not confer additional immunological children.

Language: Английский

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Vaccine-induced T cell responses control Orthoflavivirus challenge infection without neutralizing antibodies in humans

Nature Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

T cells have been identified as correlates of protection in viral infections. However, the level vaccine-induced needed and extent to which they alone can control acute infection humans remain uncertain. Here we conducted a double-blind, randomized controlled trial involving vaccination challenge 33 adult human volunteers, using live–attenuated yellow fever (YF17D) chimeric Japanese encephalitis–YF17D (JE/YF17D) vaccines. Both Orthoflavivirus vaccines share cell epitopes but different neutralizing antibody epitopes. The primary objective was assess responses, independent antibodies, were able reduce post-challenge RNAaemia levels. Secondary objectives included an assessment surrogate measures control, including titres symptomatic outcomes. YF17D vaccinees had reduced levels JE/YF17D viraemia, compared with those without previous (mean log10(area under curve genome copies per ml): 2.23 versus 3.22; P = 0.039). Concomitantly, lower post-JE/YF17D that JE virus plaque number by 50%, or PRNT50 log10(PRNT50 titre): 1.87 2.5; < 0.0001) rates (6% (n 1/16) 53% 9/17), 0.007). There no unexpected safety events. Importantly, after infection, several undetectable viraemia seroconversion, even absence antibodies. Indeed, high specifically against capsid protein, associated conventionally interpreted sterilizing immunity. Our findings reveal importance controlling suggests potential correlate orthoflaviviral ClinicalTrials.gov registration: NCT05568953 . authors demonstrate effectiveness infections, conducting study humans.

Language: Английский

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mRNA vaccines: a new opportunity for malaria, tuberculosis and HIV

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 24, 2023

The success of the first licensed mRNA-based vaccines against COVID-19 has created a widespread interest on mRNA technology for vaccinology. As expected, number in preclinical and clinical development increased exponentially since 2020, including numerous improvements formulation design, delivery methods manufacturing processes. However, faces challenges such as cost raw materials, lack standardization, optimization. MRNA may provide solution to some emerging infectious diseases well deadliest hard-to-treat malaria, tuberculosis, human immunodeficiency virus/acquired syndrome (HIV/AIDS), which an effective vaccine, easily deployable endemic areas is urgently needed. In this review, we discuss functional structure, processes vaccines. We up-to-date overview diseases, immunogenicity, efficacy correlates protection vaccines, with particular focus research tuberculosis HIV.

Language: Английский

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Defending against SARS-CoV-2: The T cell perspective

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 27, 2023

SARS-CoV-2-specific T cell response has been proven essential for viral clearance, COVID-19 outcome and long-term memory. Impaired early cell-driven immunity leads to a severe form of the disease associated with lymphopenia, hyperinflammation imbalanced humoral response. Analyses acute SARS-CoV-2 infection have revealed that mild course is characterized by an induction specific cells within first 7 days symptoms, coordinately followed antibody production effective control infection. In contrast, patients who do not develop cellular initiate immune subsequent high levels antibodies, symptoms. Yet, delayed persistent bystander CD8+ activation also reported in hospitalized could be driver lung pathology. Literature supports maintenance appears more stable than titters. Up date, virus-specific memory detected 22 months post-symptom onset, predominant IL-2 compared IFN-γ. Furthermore, responses are conserved against emerging variants concern (VoCs) while these mostly able evade responses. This partly explained HLA polymorphism whereby epitope repertoire recognized differ among individuals, greatly decreasing likelihood escape. Current COVID-19-vaccination shown elicit Th1-driven spike-specific response, as does natural infection, which provides substantial protection death. addition, mucosal vaccination induce strong adaptive both locally systemically protect VoCs animal models. The optimization vaccine formulations including variety regions, innovative adjuvants or diverse administration routes result desirable enhanced memory, help prevent breakthrough infections. summary, increasing evidence highlights relevance monitoring only levels, correlate after and/or vaccination. Moreover, it may better identify target populations benefit most from booster doses personalize strategies.

Language: Английский

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Updated Insights into the T Cell-Mediated Immune Response against SARS-CoV-2: A Step towards Efficient and Reliable Vaccines

Vaccines, Journal Year: 2023, Volume and Issue: 11(1), P. 101 - 101

Published: Jan. 1, 2023

The emergence of novel variants SARS-CoV-2 and their abilities to evade the immune response elicited through presently available vaccination makes it essential recognize mechanisms which interacts with human response. It is not only comprehend infection mechanism but also for generation effective reliable vaccines against COVID-19. effectiveness vaccine supported by adaptive response, mainly consists B T cells, play a critical role in deciding prognosis COVID-19 disease. cells are reducing viral load containing infection. A plethora proteins can be recognized provide broad range protection, especially amid SARS-CoV-2. However, hyperactivation effector reduced number lymphocytes have been found key characteristics severe Notably, excessive cell activation may cause acute respiratory distress syndrome (ARDS) producing unwarranted amounts cytokines chemokines. Nevertheless, still unknown how T-cell-mediated responses function determining Additionally, functional perturbations lead form disease protection many other infections. Hence, an updated review has developed understand involvement mechanism, turn determines Importantly, we focused on cells’ exhaustion under certain conditions these modulated therapeutic strategies discussed that elevate cell-mediated either directly or indirectly.

Language: Английский

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The immune response to SARS-CoV-2 in people with HIV

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 21(2), P. 184 - 196

Published: Oct. 11, 2023

Abstract This review examines the intersection of HIV and SARS-CoV-2 pandemics. People with (PWH) are a heterogeneous group that differ in their degree immune suppression, reconstitution, viral control. While COVID-19 those well-controlled infection poses no greater risk than for HIV-uninfected individuals, people advanced disease more vulnerable to poor outcomes. vaccines effective well tolerated majority PWH, though reduced vaccine efficacy, breakthrough infections faster waning effectiveness have been demonstrated PWH. is likely result suboptimal humoral cellular responses after vaccination. may also experience prolonged give rise new epidemiologically significant variants, but initiation or resumption antiretroviral therapy (ART) can effectively clear persistent infection. guidelines reflect these increased risks recommend prioritization vaccination additional booster doses PWH who moderately severely immunocompromised. We continued research monitoring infection, especially areas high burden.

Language: Английский

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T cell immune memory after covid-19 and vaccination

BMJ Medicine, Journal Year: 2023, Volume and Issue: 2(1), P. e000468 - e000468

Published: Nov. 1, 2023

The T cell memory response is a crucial component of adaptive immunity responsible for limiting or preventing viral reinfection. after infection with the SARS-CoV-2 virus vaccination broad, and spans multiple proteins epitopes, about 20 in each individual. So far long lasting provides high level cross reactivity hence resistance to escape by variants virus, such as omicron variant. All current vaccine regimens tested produce robust responses, heterologous will probably enhance protective responses through increased breadth. could have major role protecting against severe covid-19 disease rapid clearance early presentation presence reactive cells might this protection. likely provide ongoing protection admission hospital death, development pan-coronovirus future proof new pandemic strains.

Language: Английский

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