Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 2, 2025

Abstract Some individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained IFN-γ-independent adaptive immune response, or effective innate host clearing Mycobacterium (Mtb) without immunity. In Indonesian household contacts (n = 1347), persistently IGRA negative status was associated with presence of BCG scar, and - especially among those scar altered cells dynamics, higher heterologous ( Escherichia coli -induced) proinflammatory cytokine production, inflammatory proteins in the mitogen tube. Neither circulating concentrations Mtb -specific antibodies nor functional antibody activity at baseline follow-up. cohort adults low incidence setting, vaccination induced but only marginally affected Mtb- profiles. Our findings suggest that more efficient rather than humoral mediates early clearance . The protective effect against infection may linked priming, also termed ‘trained immunity’.

Язык: Английский

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Preclinical development of a replication-competent vesicular stomatitis virus-based Lassa virus vaccine candidate advanced into human clinical trials

EBioMedicine, Год журнала: 2025, Номер 114, С. 105647 - 105647

Опубликована: Апрель 1, 2025

SummaryBackgroundLassa fever (LF) is a zoonotic haemorrhagic disease caused by Lassa virus (LASV), which endemic in West African countries. The multimammate rat the main animal reservoir and its geographic range expected to expand due influences like climate change land usage, this will place larger parts of Africa at risk. We conducted preclinical development on promising experimental vaccine that allowed advancement into human trials.MethodsThe LF based vesicular stomatitis (VSV) vector VSV glycoprotein (G) was replaced with LASV complex (GPC). Earlier studies showed (VSVΔG-LASV-GPC) efficacious macaques, thus we regenerated VSVΔG-LASV-GPC using laboratory documentation practices required support manufacturing trials. efficacy clinical candidate assessed cynomolgus macaques more extensive immunologic analysis performed than previously investigate immune responses associated protection.FindingsA single vaccination elicited innate, humoural cellular responses, prevented substantial viraemia, protected animals from disease. Vaccinated developed polyfunctional antibodies serum shown neutralize expressing GPCs representative geographically diverse lineages.InterpretationThe immunity 10 vaccinated supporting use program, recently progressed phase 2 Moreover, virus-neutralizing likely played role preventing macaques.FundingThis work supported Coalition for Epidemic Preparedness Innovations (CEPI), National Institute Allergy Infectious Diseases (NIAID)/National Institutes Health (NIH), Bill Melinda Gates Global Vaccine Accelerator Program, Burroughs Wellcome Fund, financial gifts Nancy Zimmerman, Mark Lisa Schwartz, Terry Susan Ragon.

Язык: Английский

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Concurrent Administration of COVID-19 and Influenza Vaccines Enhances Spike-Specific Antibody Responses

Open Forum Infectious Diseases, Год журнала: 2024, Номер 11(4)

Опубликована: Март 13, 2024

Abstract Background The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, immunogenicity of concurrent vs separate administration these vaccines remains unclear. Methods Here, we analyzed antibody responses health care workers who received booster vaccine on same day or different days through systems serology. Antibody-binding functional characterized at peak after 6 months following vaccination. Results IgG1 neutralization to SARS-CoV-2 XBB.1.5 higher as compared with vaccines. While similar results not observed for responses, no interference was noted administration. Conclusions These data suggest that may yield more durable neutralizing while maintaining against influenza.

Язык: Английский

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Boosting with adjuvanted SCB-2019 elicits superior Fcγ-receptor engagement driven by IgG3 to SARS-CoV-2 spike

npj Vaccines, Год журнала: 2024, Номер 9(1)

Опубликована: Янв. 5, 2024

Abstract With the continued emergence of variants concern, global threat COVID-19 persists, particularly in low- and middle-income countries with limited vaccine access. Protein-based vaccines, such as SCB-2019, can be produced on a large scale at low cost while antigen design adjuvant use modulate efficacy safety. While effective humoral immunity against SARS-CoV-2 has been shown to depend both neutralization Fc-mediated immunity, data effectiveness protein-based vaccines enhanced is limited. Here, we assess profile, including antibody isotypes, subclasses, Fc receptor binding generated by boosting recombinant trimer-tag protein SCB-2019. Individuals who were primed 2 doses ChAdOx1 equally divided into 4 groups boosted following formulations: Group 1: 9 μg SCB-2019 Alhydrogel; 2: CpG 1018, 3: 30 4: ChAdOx1. 3 showed FcγR wild-type compared Groups 1 2, showing dose-dependent enhancement conferred vaccine. Moreover, from day 15 after vaccination, exhibited higher IgG3 across concerns, Omicron its subvariants, ChAdOx1-boosted individuals. Overall, this highlights potential cost-efficient regimen concerns.

Язык: Английский

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Heterologous Ad26/Ad5 adenovirus-vectored vaccines elicited SARS-CoV-2-specific antibody responses with potent Fc activities

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Май 8, 2024

Introduction Antibodies against the SARS-CoV-2 spike protein are a critical immune determinant for protection virus. While virus neutralization is key function of spike-specific antibodies, antibodies also mediate Fc-dependent activities that can play role in or pathogenesis. Methods This study characterized serum antibody responses elicited after two doses heterologous adenovirus-vectored (Ad26/ Ad5) vaccines. Results Vaccine-induced binding titers and Fc-mediated functions decreased over six months, while remained stable. Comparison isotypes Ad26/Ad5 vs. LNP-mRNA vaccination infection showed anti-spike IgG1 were dominant produced to high levels all groups. The vaccines induced IgG4 but not IgG2 IgG3, whereas full Ig spectrum (IgM, IgG1-4, IgA1-2). Convalescent COVID-19 patients had mainly IgM IgA1 alongside IgG1. Despite these differences, potencies early variants similar. However, both vaccine groups with greater Fc complement Fcg receptors than group. group displayed potency RBD-specific antibody-mediated cellular phagocytosis. Discussion distinctive quality by different infection. data imply utility platforms elicit fine-tuned activities.

Язык: Английский

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Antibodies as key mediators of protection against Mycobacterium tuberculosis

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Сен. 2, 2024

Tuberculosis (TB) is caused by infection with the bacterial pathogen Mycobacterium tuberculosis (M.tb) in respiratory tract. There was an estimated 10.6 million people newly diagnosed TB, and there were approximately 1.3 deaths TB 2022. Although global prevalence of has remained high for decades annual leading cause death attributed to infectious diseases, only one vaccine, Bacillus Calmette–Guérin (BCG), been approved so far prevent/attenuate disease. Correlates protection or immunological mechanisms that are needed control M.tb remain unknown. The protective role antibodies after BCG vaccination also largely unclear; however, recent studies have provided evidence their involvement against disease, as biomarkers state infection, potential predictors outcomes. Interestingly, generated post-vaccination linked activation innate immune cascades, providing further antibody effector functions critical pathogens such M.tb. In this review, we aim provide current knowledge application diagnosis, prevention, treatment. Particularly, review will focus on 1) preventing infections through Mtb adherence epithelium, antibody-mediated phagocytosis, cellular cytotoxicity; 2) M.tb-directed response how humoral profiles different glycosylation patterns these disease state; 3) How immunity can be explored early diagnosis detection methods combat burden. Broadening paradigm differentiated profiling antibody-based during progression offers new directions treatment, preventative strategies. This approach involves linking aforementioned responses state, progression, clearance.

Язык: Английский

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Compartment-specific antibody correlates of protection to SARS-CoV-2 Omicron in macaques

iScience, Год журнала: 2024, Номер 27(9), С. 110174 - 110174

Опубликована: Июнь 5, 2024

Antibodies represent a primary mediator of protection against respiratory viruses. Serum neutralizing antibodies (NAbs) are often considered correlate protection. However, detailed antibody profiles including characterization functions in different anatomic compartments poorly understood. Here we show that correlates severe acute syndrome coronavirus 2 (SARS-CoV-2) challenge systemic versus mucosal rhesus macaques. In serum, NAbs were the strongest and linked to spike-specific binding other extra-NAb create larger protective network. bronchiolar lavage (BAL), antibody-dependent cellular phagocytosis (ADCP) proved rather than NAbs. Within BAL, ADCP was immunoglobulin (Ig)G, IgA/secretory IgA, Fcγ-receptor antibodies. Our results support model which with mediate at sites.

Язык: Английский

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Dissecting humoral immune responses to an MVA-vectored MERS-CoV vaccine in humans using a systems serology approach

iScience, Год журнала: 2024, Номер 27(8), С. 110470 - 110470

Опубликована: Июль 8, 2024

Besides neutralizing antibodies, which are considered an important measure for vaccine immunogenicity, Fc-mediated antibody functions can contribute to antibody-mediated protection. They strongly influenced by structural properties such as subclass and Fc glycan composition. We here applied a systems serology approach dissect humoral immune responses induced MVA-MERS-S, MVA-vectored against the Middle East respiratory syndrome coronavirus (MERS-CoV). Building on preceding studies reporting safety immunogenicity of our study highlights potential late boost, administered one year after prime, enhance both functionality compared primary vaccination series. Distinct characteristics were observed antibodies specific MERS-CoV spike protein S1 S2 subunits, regarding compositions well functionality. These findings highlight benefit homologous booster with MVA-MERS-S may be interest design future vaccines.

Язык: Английский

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Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 21, 2024

Abstract Some individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained IFN-γ-independent adaptive immune response, or effective innate host clearing Mycobacterium (Mtb) without immunity. In Indonesian household contacts (n=1347), persistently IGRA negative status was associated with presence of BCG scar, and - especially among BCG-vaccinated individuals altered cells dynamics, higher heterologous ( Escherichia coli -induced) proinflammatory cytokine production, inflammatory proteins in the mitogen tube. Neither circulating concentrations Mtb -specific antibodies nor functional antibody activity at baseline follow-up. cohort adults low incidence setting, vaccination induced but only marginally affected Mtb- profiles. Our findings suggest that more efficient rather than humoral mediates early clearance . The protective effect against infection may linked priming, also termed ‘trained immunity’.

Язык: Английский

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Defining correlates of protection for mammalian livestock vaccines against high-priority viral diseases

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 19, 2024

Enhancing livestock biosecurity is critical to safeguard the livelihoods of farmers, global and local economies, food security. Vaccination fundamental control prevention exotic endemic high-priority infectious diseases. Successful implementation vaccination in a plan underpinned by strong understanding correlates protection—those elements immune response that can reliably predict level protection from viral challenge. While have been successfully characterized for many human vaccines, diseases, including African swine fever foot mouth disease, they remain largely uncharacterized. Current literature provides insights into potential should be assessed during vaccine development these mammalian Establishment purposes enables surveillance, rationale development, successful vaccines as part strategy.

Язык: Английский

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