Global domination of the recently VoI-classified 'JN.1′ outcompeting other variants – Comparing the vaccines’ efficacy

Clinical Infection in Practice, Journal Year: 2024, Volume and Issue: 22, P. 100358 - 100358

Published: April 1, 2024

Language: Английский

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A Next-Generation Adenoviral Vaccine Elicits Mucosal and Systemic Immunogenicity and Reduces Viral Shedding after SARS-CoV-2 Challenge in Nonhuman Primates

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 132 - 132

Published: Jan. 27, 2024

As new SARS-CoV-2 variants continue to emerge and impact communities worldwide, next-generation vaccines that enhance protective mucosal immunity may have a significant on productive infection transmission. We developed recombinant non-replicating adenovirus serotype 5 (rAd5) delivered by administration express both target antigen novel molecular adjuvant within the same cell. Here, we describe immunogenicity of three unique rAd5 vaccine candidates their efficacy following viral challenge in non-human primates (NHPs). Intranasal immunization with expressing Wuhan, or Beta variant spike alone, Wuhan nucleocapsid elicited strong antigen-specific serum IgG IgA neutralizing activity against multiple concern (VOC). Robust cross-reactive was detected after single rAd5, which showed VOC. Additionally, vaccination increased spike-specific IFN-γ producing circulating T-cells. Upon challenge, all vaccinated NHPs exhibited reductions load infectious particle shedding nasal passages lower airways. These findings demonstrate is highly immunogenic, confers antibody responses circulation mucosa, reduces challenge.

Language: Английский

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Establishment of the First National Standard for Neutralizing Antibodies against SARS-CoV-2 XBB Variants

Viruses, Journal Year: 2024, Volume and Issue: 16(4), P. 554 - 554

Published: April 1, 2024

Neutralizing antibodies (NtAbs) against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are indicators of vaccine efficacy that enable immunity surveillance. However, the rapid mutation SARS-CoV-2 variants prevents timely establishment standards required for effective XBB evaluation. Therefore, we prepared four candidate (No. 11, No. 44, 22, and 33) using plasma, purified immunoglobulin, a broad-spectrum neutralizing monoclonal antibody. Collaborative calibration was conducted across nine Chinese laboratories neutralization methods 11 strains containing BA.2.86 sublineages. This study demonstrated reduced potency first International Standard to concern variants. 44 displayed activity sublineages, effectively interlaboratory variability nearly all variants, minimized geometric mean titer (GMT) difference between live pseudotyped virus. 22 showed broader spectrum higher but failed reduce variability. Thus, approved as National NtAbs providing unified NtAb measurement standard time. Moreover, national reference reagent SARS-CoV-2, offering current potentially emerging

Language: Английский

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Nasal mucosal secretory IgA but not serum antibodies is resistant to Omicron evasion

hLife, Journal Year: 2024, Volume and Issue: 2(9), P. 488 - 491

Published: May 21, 2024

Language: Английский

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Comparative immunogenicity of monovalent and bivalent adenovirus vaccines carrying spikes of early and late SARS-CoV-2 variants

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: 13(1)

Published: July 31, 2024

The continuous emergence of highly immune-evasive SARS-CoV-2 variants has challenged vaccine efficacy. A that can provide broad protection is desirable. We evaluated the immunogenicity a series monovalent and bivalent adenovirus-vectored vaccines containing spikes Wildtype (WT), Beta, Delta, Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.2.13, BA.3, BA.5, BQ.1.1, XBB. Vaccination in mice using elicited highest neutralizing titers against each self-matched strain, but other were reduced 2- to 73-fold. consisting WT BA.5 broadened breadth pre-Omicron except Among based on strains before XBB, BA.2 most potent antibodies subvariants, including In primed with injected vaccine, intranasal booster XBB could elicit serum respiratory mucosal all late had been sequentially vaccinated greater than Both induced EG.5. Unlike antibody response, which variant-specific, receiving either or comparable T-cell responses variants. Furthermore, not intramuscular antigen-specific lung resident T cells. This study provides insights into design COVID-19 vaccination strategies.

Language: Английский

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Heterogeneity of SARS-CoV-2 immune responses after the nationwide Omicron wave in China

Microbiology Spectrum, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 17, 2024

ABSTRACT It remains unclear how previous infections and vaccinations influenced shaped heterogeneous immune responses against Omicron its variants in diverse populations China. After the national wave of early 2023, we evaluated serum levels neutralizing antibodies (nAbs) (B.1.1.529) (BA.5, BF.7, CH1.1) 33 COVID-19 convalescents 40 uninfected vaccinees, using vesicular stomatitis virus-based pseudovirus assay. In addition, followed 34 Delta convalescent patients to compare their before (late 2021) after (early 2023). NAbs at acute phase disease were investigated 50 inpatients, including 24 vaccinated 26 unvaccinated patients. Among them, nasal mucosal IgA measured 42 subjects. Compared vaccination, breakthrough significantly increased breadth magnitude nAbs variants. Exposure but not elicited stronger pan-Omicron responses. continued rise as vaccination doses increased. However, both vaccinees convalescents, a fourth dose did elicit higher Omicron. Furthermore, lasted longer than WT SARS-CoV-2. Breakthrough specific compared infection. Although repeated revealed limited impacts on nAbs, high risk hospitalization may still benefit from vaccination. IMPORTANCE The study described humoral immunity populations, Delta-positive patients, Omicron-infected with or current confirmed infection, Omicron-positive healthy controls. for 1 year evaluate effect booster vaccine, reinfection. Nasal SARS-CoV-2 also examined. findings this demonstrated varied individuals different states following outbreak Omicron, highlighting potential advantages ongoing immunization groups that are more vulnerable have greater likelihood being hospitalized.

Language: Английский

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Antibodies in breast milk: Pro‐bodies designed for healthy newborn development

Immunological Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 22, 2024

This manuscript sheds light on the impact of maternal breast milk antibodies infant health. Milk prepare and protect newborn against environmental exposure, guide regulate offspring's immune system, promote transgenerational adaptation system to its environment. While transfer IgG across placenta ceases at birth, are continuously replenished by system. They reflect mother's real-time environment which is exposed. cover infant's upper respiratory digestive mucosa perfectly positioned control responses antigens might also reach their circulation. Maternal in play a key role defense developing child, with major infectious disease susceptibility both HIC LMIC. influence development another health burden children-allergies. Finally, emerging evidence shows that actively shape development. Much this likely be mediated effect seeding, composition function microbiota, but not only. Further understanding bridge provide between child should enable best interventions healthy

Language: Английский

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Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 25, 2024

Unlocking the potential of broadly reactive coronavirus monoclonal antibodies (mAbs) and their derivatives offers a transformative therapeutic avenue against severe COVID-19, especially crucial for safeguarding high-risk populations. Novel mAb-based immunotherapies may help address reduced efficacy current vaccines neutralizing mAbs caused by emergence variants concern (VOCs). Using phage display technology, we discovered pan-SARS-CoV-2 mAb (C10) that targets conserved region within receptor-binding domain (RBD) virus. Noteworthy, C10 demonstrates exceptional in recognizing all assessed VOCs, including recent Omicron variants. While lacks direct neutralization capacity, it efficiently binds to infected lung epithelial cells induces lysis via natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Building upon this mAb, engineered C10-based, Chimeric Antigen Receptor (CAR)-T endowed with efficient killing capacity SARS-CoV-2-infected cells. Notably, NK CAR-T-cell mediated effectively reduces viral titers. These findings highlight non-neutralizing providing immune protection emerging infectious diseases. Our work reveals effective targeting proof-of-concept application CAR-T cell therapy combating SARS-CoV-2 infections. Furthermore, holds promise development innovative antibody-based cell-based strategies COVID-19 expanding array options available populations.Trial registration: ClinicalTrials.gov identifier: NCT04093596.

Language: Английский

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Ultrapotent IgA dimeric antibodies neutralize emerging Omicron variants

Journal of Virology, Journal Year: 2024, Volume and Issue: 99(1)

Published: Dec. 4, 2024

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Induction of Tier 2 HIV-Neutralizing IgA Antibodies in Rhesus Macaques Vaccinated with BG505.664 SOSIP

Vaccines, Journal Year: 2024, Volume and Issue: 12(12), P. 1386 - 1386

Published: Dec. 10, 2024

A goal of mucosal human immunodeficiency virus type 1 (HIV-1) vaccines is to generate plasma cells producing polymeric IgA (pIgA)-neutralizing antibodies at sites viral entry. However, vaccine immunogens capable eliciting neutralizing (nAbs) that recognize tier 2 isolates have not yet been identified. To determine if stabilized native-like HIV-1 envelope (Env) trimers could nAbs, we purified total and IgG from the banked sera six rhesus macaques had found in a previous study develop serum nAbs after subcutaneous immunization with BG505.664 SOSIP 3M-052 adjuvant, which TLR7/8 agonist. The neutralization autologous BG505 T332N pseudovirus by preparations was measured using TZM-bl assay. Anti-SOSIP binding (bAbs) were ELISA. samples significantly greater levels both nAb bAb. normalizing titer relative concentration bAb, SOSIP-specific 2/6 animals neutralize just as effectively IgG, 3/6 animals, specific greater. more potent these three associated higher percentage anti-SOSIP J chain-bound (polymeric) antibody. parenteral vaccination nonhuman primates generates serum, including IgA, appears efficiently than monomeric or IgG. Mucosal delivery this other stable Env locally synthesized tissues secretions.

Language: Английский

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