ACE2 decoy Fc-fusions and bi-specific killer engager (BiKEs) require Fc engagement for in vivo efficacy against SARS-CoV-2 DOI Open Access
Jenna K. Dick, Dustin Hicks, Venkatramana D. Krishna

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 21, 2024

Abstract SARS-CoV-2 virus has continued to evolve over time necessitating the adaptation of vaccines maintain efficacy. Monoclonal antibodies (mAbs) against were a key line defense for unvaccinated or immunocompromised individuals. However, these mAbs are now ineffective current variants. Here, we tested three aspects αSARS-CoV-2 therapeutics. First, whether Fc engagement is necessary in vivo clearance SARS-CoV-2. Secondly, bi-specific killer engagers (BiKEs) that simultaneously engage and specific receptor. Benefits include ease manufacturing, stability, more cell-specific targeting, high affinity binding receptors. Using both BiKEs, found neutralization receptor effective clearance. Thirdly, due ACE2 being viral entry, will despite evolution. Therefore, used an decoy Fc-fusion BiKE, instead anti-SARS-CoV-2 antibody sequence, as potential therapeutic would withstand We approach also required and, unlike traditional neutralizing variants, enabled two distinct These data show importance mAbs, utility BiKEs therapies infectious disease, effectiveness approach. With further studies, predict combining neutralization, cellular response, this benefit individuals with levels. Abbreviations ACE2, scFv, mAb, COVID-19, Fc, CD16, CD32b, CD64, d.p.i Key points equal dosing, optimal efficacy can clear protect severe infection hACE2-K18 mouse model. decoys part Fc-fusions provide disparate

Language: Английский

Progress and Challenges in HIV-1 Vaccine Research: A Comprehensive Overview DOI Creative Commons
Alex Boomgarden, Chitra Upadhyay

Vaccines, Journal Year: 2025, Volume and Issue: 13(2), P. 148 - 148

Published: Jan. 31, 2025

The development of an effective HIV-1 vaccine remains a formidable challenge in biomedical research. Despite significant advancements our understanding HIV biology and pathogenesis, progress has been impeded by factors such as the virus's genetic diversity, high mutation rates, its ability to establish latent reservoirs. Recent innovative approaches, including mosaic vaccines mRNA technology induce broadly neutralizing antibodies, have shown promise. However, efficacy these modest, with best results achieving approximately 30% effectiveness. Ongoing research emphasizes necessity multifaceted strategy overcome obstacles achieve breakthrough development. This review summarizes current approaches utilized further understand create global vaccine. We discuss impact on for other diseases, COVID-19, influenza, Zika virus. Additionally, we highlight specific limitations faced each approach present methods researchers employ challenges. These techniques, which demonstrated preclinical clinical success, advanced field closer ultimate goal developing Leveraging will enable strides combating infectious ultimately improving health outcomes.

Language: Английский

Citations

3
Deciphering Host–Virus Interactions and Advancing Therapeutics for Chronic Viral Infection DOI Creative Commons
Majid Eslami,

Neda Arjmand,

Fatemeh Mahmoudian

et al.

Viruses, Journal Year: 2025, Volume and Issue: 17(3), P. 390 - 390

Published: March 10, 2025

Chronic viral infections like HIV, HBV, and HCV establish persistent interactions with the host immune system, resulting in evasion long-term dysfunction. These viruses use a range of strategies to limit defenses, such as downregulating MHC class I, disrupting interferon signaling, altering apoptosis pathways, suppressing cytotoxic T-cell activity. Key proteins, including HIV Nef, HBV X protein, NS5A, interfere antigen presentation JAK/STAT thereby reducing antiviral responses. induce exhaustion due exposure, which leads expression inhibitory receptors PD-1 CTLA-4 on T cells. Viral epigenetic changes, N6-methyladenosine modifications histone deacetylation, enhance by modulating gene infected Viruses further manipulate cytokine networks promoting an immunosuppressive environment through IL-10 TGF-β secretion, suppress inflammatory responses inhibit activation. This review examines molecular/cellular mechanisms that enable chronic escape immunity, focusing antigenic variation, disruption, control apoptotic pathways. It also addresses how genetic factors, HLA polymorphisms, influence disease progression. Lastly, we discuss host-targeted therapies, checkpoint inhibitors, treatments, CRISPR.

Language: Английский

Citations

2
Gaston Ramon’s Big Four DOI Creative Commons
Jean‐Philippe Chippaux

Toxins, Journal Year: 2024, Volume and Issue: 16(1), P. 33 - 33

Published: Jan. 9, 2024

When immunology was still in its infancy, Gaston Ramon made several major contributions to humoral [...].

Language: Английский

Citations

6
Persistence of IgG and neutralizing antibodies in Crimean−Congo hemorrhagic fever survivors DOI

Abbas Ahmadi Vasmehjani,

Mohammad Hassan Pouriayevali, Shohreh Shahmahmoodi

et al.

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(4)

Published: April 1, 2024

Abstract The World Health Organization classified Crimean–Congo hemorrhagic fever (CCHF) as a high‐priority infectious disease and emphasized the performance of research studies product development against it. Little information is available about immune response due to natural CCHF virus (CCHFV) infection in humans. Here, we investigated persistence IgG neutralizing antibodies serum samples collected from 61 Iranian survivors with various time points after recovery (<12, 12−60, >60 months disease). ELISA results showed seropositivity all while pseudotyped based neutralization assay findings revealed presence antibody 29 (46.77%). For both antibodies, decreasing trend titer was observed increase recovery. Not only mean (772.80 U/mL) higher than (25.64) but also longer. In conclusion, our provide valuable long‐term humoral indicating that can be detected at least 8 years low titers survivors.

Language: Английский

Citations

5
Beyond bnAbs: Uses, Risks, and Opportunities for Therapeutic Application of Non-neutralising Antibodies in Viral Infection DOI Open Access
Kahlio Mader, Lynn B. Dustin

Published: March 29, 2024

The vast majority of antibodies generated against a virus will be non-neutralising1. However, this does not denote an absence protective capacity. Yet, within the field there is typically large focus on capable directly blocking infection (neutralising antibodies, nAbs) either specific viral strains or multiple (broadly-neutralising bnAbs). More recently, non-neutralising (nnAbs), neutralisation-independent effects nAbs, has emerged. These can have additive protection in some cases, major correlate protection. As their name suggests, nnAbs do neutralise but instead, through Fc domains, may mediate interaction with other immune effectors to induce clearance particles virally infected cells. also interrupt replication Developing technologies antibody modification and functionalisation lead innovative biologics that harness activities for antiviral prophylaxis therapeutics. In review, we discuss examples nnAb actions infections where they known importance. We potential detrimental such responses. Finally, explore new increase efficacy introduce favourable characteristics therapeutic applications.

Language: Английский

Citations

3
Comparative Analysis of Vaccine-Induced Neutralizing Antibodies against the Alpha, Beta, Delta, and Omicron Variants of SARS-CoV-2 DOI Creative Commons
Philipp Girl, Heiner von Buttlar,

Enrico Mantel

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(5), P. 515 - 515

Published: May 9, 2024

The SARS-CoV-2 virus has infected more than 660 million people and caused nearly seven deaths worldwide. During the pandemic, a number of vaccines were rapidly developed, several are currently licensed for use in Europe. However, optimization vaccination regimens is still ongoing, particularly with regard to booster vaccinations. At same time, emergence new variants poses an ongoing challenge vaccine efficacy. In this study, we focused on comparative analysis neutralization capacity vaccine-induced antibodies against four different concern (i.e., Alpha, Beta, Delta, Omicron) after two three doses COVID-19 vaccine. We able show that both (prime/boost) (prime/boost/boost) vaccinations elicit highly variable levels neutralizing antibodies. addition, did not observe significant difference antibody also observed decrease susceptibility all but one contrast, breakthrough infection between second third results overall higher concomitant improved variants. Titer remained across cohort common trend was observed. This may be due fact at time based exclusively wild-type SARS-CoV-2, whereas infections by Overall, our data demonstrate importance (booster) vaccinations, emphasize need continued adaptation induce protective immune response order prepared future (seasonal) outbreaks.

Language: Английский

Citations

3
Anti-RBD Antibody Levels and IFN-γ-Specific T Cell Response Are Associated with a More Rapid Swab Reversion in Patients with Multiple Sclerosis after the Booster Dose of COVID-19 Vaccination DOI Creative Commons
Alessandra Aiello, Serena Ruggieri, Assunta Navarra

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(8), P. 926 - 926

Published: Aug. 19, 2024

This study investigated the incidence and severity of SARS-CoV-2 breakthrough infections (BIs) time to swab reversion in patients with multiple sclerosis (PwMS) after booster dose COVID-19 mRNA vaccines. We enrolled 64 PwMS who had completed three-dose vaccine schedule never experienced before. Among PwMS, 43.8% BIs a median since third 155 days. occurred more frequently ocrelizumab-treated (64.7%). Patients relapsing-remitting MS course showed reduced compared those primary-progressive disease (

Language: Английский

Citations

3
Long-term immune responses induced by low-dose infection with high pathogenicity avian influenza viruses can protect mallards from reinfection with a heterologous strain DOI Creative Commons
Saki Sakuma, Junki Mine, Yuko Uchida

et al.

Archives of Virology, Journal Year: 2025, Volume and Issue: 170(2)

Published: Jan. 9, 2025

Migratory water birds are considered to be carriers of high pathogenicity avian influenza viruses (HPAIVs). In Japan, mallards often observed during winter, and HPAIV-infected shed asymptomatically. this study, we focused on as potential HPAIVs investigated whether individual wild repeatedly infected with act HPAIV multiple times within a season. Mallards were experimentally H5N1 H5N8 that isolated recently in Japan phylogenetically belong different hemagglutinin groups (G2a, G2b, G2d). All these strains more infectious than chickens, the enough virus infect others, regardless they exhibited clinical signs. Serum antibodies homologous antigen, induced by single infection low dose (10 50% mallard dose), maintained at detectable levels for 84 days. Immunity days post-inoculation fully protected from challenge strain, demonstrated lack viral shedding, antibody did not increase significantly most birds. Protection against heterologous was also despite undetectable strain. Our findings suggest repeated infections do occur frequently season, particularly doses, frequency which may limited.

Language: Английский

Citations

0
Porcine antibodies reveal novel non-neutralizing universal epitopes on FMDV and their overlaps with neutralization sites DOI

Ying Sun,

Shenglin Huang,

Fengjuan Li

et al.

Veterinary Microbiology, Journal Year: 2025, Volume and Issue: 303, P. 110440 - 110440

Published: Feb. 24, 2025

Language: Английский

Citations

0
A novel tetravalent influenza vaccine based on one chimpanzee adenoviral vector DOI

Yixin Niu,

Yao Yan,

Ying Hu

et al.

Vaccine, Journal Year: 2025, Volume and Issue: 53, P. 126959 - 126959

Published: March 1, 2025

Language: Английский

Citations

0