Infectious Disease Clinics of North America, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Язык: Английский
Nature Immunology, Год журнала: 2024, Номер 25(3), С. 537 - 551
Опубликована: Фев. 9, 2024
Abstract A nasally delivered chimpanzee adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (ChAd-SARS-CoV-2-S) is currently used in India (iNCOVACC). Here, we update this by creating ChAd-SARS-CoV-2-BA.5-S, which encodes a prefusion-stabilized BA.5 spike protein. Whereas serum neutralizing antibody responses induced monovalent or bivalent adenoviral vaccines were poor against the antigenically distant XBB.1.5 strain and insufficient to protect passive transfer experiments, mucosal cross-reactive memory T cell robust, protection was evident WA1/2020 D614G Omicron variants BQ.1.1 mice hamsters. However, depletion of CD8 + cells before challenge resulted loss upper lower tract infection. Thus, stimulate immunity emerging SARS-CoV-2 strains, mediate lung infection strains setting low levels antibodies.
Язык: Английский
Процитировано
16
Cellular and Molecular Immunology, Год журнала: 2023, Номер 21(2), С. 144 - 158
Опубликована: Ноя. 10, 2023
Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 prompted scientific, medical, and biotech communities to investigate infection- vaccine-induced immune responses the context this pathogen. B-cell antibody are at center these investigations, as neutralizing antibodies (nAbs) an important correlate protection (COP) from infection primary target SARS-CoV-2 vaccine modalities. In addition absolute levels, nAb longevity, neutralization breadth, immunoglobulin isotype subtype composition, presence mucosal sites have become topics for scientists health policy makers. recent pandemic was still is a unique setting which study de novo memory (MBC) dynamic interplay immunity. It also provided opportunity explore new platforms, such mRNA or adenoviral vector vaccines, unprecedented cohort sizes. Combined with technological advances years, situation has detailed mechanistic insights into development but revealed some unexpected findings. review, we summarize key findings last 2.5 years regarding immunity, believe significant value not only future vaccination approaches endemic settings.
Язык: Английский
Процитировано
36
Cell Reports, Год журнала: 2023, Номер 42(8), С. 112888 - 112888
Опубликована: Июль 31, 2023
Evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has led to emergence sublineages with different patterns neutralizing antibody evasion. We report that BA.4/BA.5 breakthrough infection individuals immunized SARS-CoV-2 wild-type-strain-based mRNA vaccines results in a boost BA.4.6, BF.7, BQ.1.1, and BA.2.75 neutralization but does not efficiently BA.2.75.2, XBB, or XBB.1.5 neutralization. In silico analyses showed spike glycoprotein lost most B cell epitopes, especially XBB.1.5. contrast, T epitopes are conserved across variants including responses mRNA-vaccinated, SARS-CoV-2-naive against wild-type strain, BA.1, were comparable, suggesting immunity recent may remain largely unaffected. While some effectively evade immunity, spike-protein-specific due nature polymorphic cell-mediated immune responses, continue contribute prevention/limitation COVID-19 manifestation.
Язык: Английский
Процитировано
23
PLoS Pathogens, Год журнала: 2024, Номер 20(6), С. e1011569 - e1011569
Опубликована: Июнь 20, 2024
Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be non-neutralizing, yet it protected mice cynomolgus macaques from severe disease. The mechanisms of NTD antibody-mediated protection are unknown. Here we show Fc mediate (non-nAb) MA10 viral challenge in mice. Though non-nAb prophylactic infusion did not suppress infectious titers lung as potently (nAb) infusion, disease markers including gross discoloration were similar nAb groups. functional knockout substitutions abolished increased group. enhancement relative WT, supporting a positive association between functionality degree infection. For therapeutic administration antibodies, contributed virus suppression lessening discoloration, but presence neutralization required for optimal This study demonstrates non-nAbs can utilize Fc-mediated lower load prevent damage due coronavirus
Язык: Английский
Процитировано
12
Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(3)
Опубликована: Янв. 10, 2024
A growing body of evidence shows that fragment crystallizable (Fc)-dependent antibody effector functions play an important role in protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To unravel the mechanisms drive these responses, we analyzed phagocytosis and complement deposition mediated by a panel 482 human monoclonal antibodies (nAbs) neutralizing original Wuhan virus, expressed as recombinant IgG1. Our study confirmed nAbs no longer SARS-CoV-2 Omicron variants can retain their Fc functions. Surprisingly, found with most potent function recognize N-terminal domain, followed those targeting class 3 epitopes receptor binding domain. Interestingly, direct against 1/2 motif, which are were weakest The divergent properties function-mediating use different B cell germlines observation polyclonal sera differ profile observed nAbs, suggesting non-neutralizing also contribute to These data provide high-resolution picture Fc-antibody response suggest contribution should be considered for design improved vaccines, selection therapeutic antibodies, evaluation correlates protection.
Язык: Английский
Процитировано
10
iScience, Год журнала: 2024, Номер 27(3), С. 109273 - 109273
Опубликована: Фев. 20, 2024
Completion of a COVID-19 vaccination series during pregnancy effectively reduces hospitalization among infants less than 6 months age. The dynamics transplacental transfer maternal vaccine-induced antibodies, and their persistence in at 2, 6, 9, 12 months, have implications for new vaccine development optimal timing administration pregnancy. We evaluated anti-COVID antibody IgG subclass, Fc-receptor binding profile, activity against wild-type Spike RBD plus five variants concern (VOCs) 153 serum samples from 100 infants. Maternal IgG1 IgG3 responses persisted 2- 6-month to greater extent the other subclasses, with high antibodies placental neonatal FcγR3A. Lowest was observed Omicron RBD-specific region. timing, capabilities, fetal sex, VOC all impact through
Язык: Английский
Процитировано
8
Trends in Immunology, Год журнала: 2024, Номер 45(8), С. 609 - 624
Опубликована: Июль 20, 2024
Recent studies show an important role for non-neutralizing anti-spike antibodies, including monoclonal antibodies (mAbs), in robustly protecting against SARS-CoV-2 infection. These mAbs use Fc-mediated functions such as complement activation, phagocytosis, and cellular cytotoxicity. There is untapped potential using durable antibody treatments; because of their available conserved epitopes, they may not be sensitive to virus mutations neutralizing mAbs. Here, we discuss evidence mAb-mediated protection We explore how mAb can enhanced via novel antibody-engineering techniques. Important questions remain answered regarding the characteristics protective mAbs, models assays used study, risks ensuing detrimental inflammation, well durability mechanisms protection.
Язык: Английский
Процитировано
8
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(1), С. 407 - 407
Опубликована: Янв. 5, 2025
Respiratory viral infections continue to cause pandemic and epidemic outbreaks in humans animals. Under steady-state conditions, alveolar macrophages (AlvMϕ) fulfill a multitude of tasks order maintain tissue homeostasis. Due their anatomic localization within the deep lung, AlvMϕ are prone detect react inhaled viruses thus play role early pathogenesis several respiratory infections. Here, detection pathogens causes diverse antiviral proinflammatory reactions. This fact not only makes them promising research targets, but also suggests as potential targets for therapeutic prophylactic approaches. review aims give comprehensive overview current knowledge about
Язык: Английский
Процитировано
1
Cell Host & Microbe, Год журнала: 2023, Номер 31(12), С. 1961 - 1973.e11
Опубликована: Ноя. 20, 2023
Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with antigenicity their spike (S) glycoproteins remain uncharacterized. Here, we show that African bat sarbecovirus PRD-0038 S has a broad angiotensin-converting enzyme 2 (ACE2) usage and receptor-binding domain (RBD) mutations further expand promiscuity enable human ACE2 utilization. We determine cryo-EM structure RBD bound to alcyone ACE2, explaining highlighting differences SARS-CoV-1 SARS-CoV-2. Characterization using monoclonal antibody reactivity reveals its distinct relative SARS-CoV-2 identifies cross-neutralizing antibodies for pandemic preparedness. vaccination elicits greater titers cross-reacting vaccine-mismatched 1a sarbecoviruses compared due broader antigenic targeting, motivating inclusion antigens in next-generation vaccines enhanced resilience viral evolution.
Язык: Английский
Процитировано
20
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Апрель 27, 2024
Abstract Streptococcus pyogenes can cause invasive disease with high mortality despite adequate antibiotic treatments. To address this unmet need, we have previously generated an opsonic IgG1 monoclonal antibody, Ab25, targeting the bacterial M protein. Here, engineer IgG2-4 subclasses of Ab25. Despite having reduced binding, IgG3 version promotes stronger phagocytosis bacteria. Using atomic simulations, show that IgG3’s Fc tail has extensive movement in 3D space due to its extended hinge region, possibly facilitating interactions immune cells. We replaced four different IgG3-hinge segment subclasses, IgGh xx . Hinge-engineering does not diminish binding as but enhances function, where a 47 amino acid is comparable function. shows improved protection against S. systemic infection mouse model, suggesting promise preclinical therapeutic candidate. Importantly, enhanced function generalizable diverse strains from clinical isolates. versions anti-SARS-CoV-2 mAbs broaden biological applicability, and these also exhibit strongly compared subclass. The subclass two distant systems provides new insights into antibody
Язык: Английский
Процитировано
6