The formulation was reconstituted with sterile water for injection to 150 mg/mL with a pH of 6.0. == Study intervention == Participants were administered VIR-2482 or volume-matched placebo as an IM injection in dorsogluteal or ventrogluteal sites. had Grade 1 or 2 2 AEs that were considered to be related to the study intervention. There were no treatment-related serious AEs. Injection-site reactions (ISRs) were reported in six (7.5%) VIR-2482 recipients, while no such reactions were reported among the placebo recipients. All Furosemide ISRs were Grade 1, and there was no relationship with the dose. Median VIR-2482 serum elimination Furosemide half-life ranged from 56.7 to 70.6 days across cohorts. The serum area under the curve andCmaxwere dose-proportional. Nasopharyngeal VIR-2482 concentrations were approximately 2%5% of serum levels and were less than dose-proportional. The incidence of immunogenicity across all cohorts was 1.3%. Overall, the safety, tolerability, and pharmacokinetic profile of VIR-2482 at doses up to 1 1,800 mg supported its further investigation as a long-acting antibody for the prevention of influenza A illness. This study has been registered at ClinicalTrials.gov under identifierNCT04033406. KEYWORDS:VIR-2482, influenza, monoclonal antibodies, prophylaxis, human immunoglobulin G1 == INTRODUCTION == Influenza viruses are single-stranded, negative-sense, segmented RNA viruses in theOrthomyxoviridaefamily, which cause highly contagious respiratory illness (1). Influenza epidemics occur annually and result in substantial morbidity and mortality. According to the World Health Organization, each year seasonal influenza causes an estimated 3 to 5 5 million cases of severe disease requiring hospitalization and 290,000 to 650,000 deaths worldwide (2). Additionally, pandemic influenza Furosemide strains arise unpredictably through genetic recombination in animals and have the potential to cause catastrophic public health emergencies, such as the 1918 influenza pandemic, which was estimated to have killed up to 50 million people. Influenza circulating within the human population is divided into Group A and B viruses, with Influenza A Virus (IAV) responsible for 70%90% of seasonal infections and all known influenza pandemics (1). The majority of people infected with seasonal IAV recover without medical care; however, certain populations are at heightened risk of serious disease and death, including children under the age of 6 months, adults over the age of 65 years, and individuals of any age with comorbidities including compromised immunity, chronic obstructive pulmonary disease, asthma, or kidney disease (2). Unlike seasonal influenza, pandemic strains have historically caused high rates of serious illness and death in young and healthy populations. The cornerstone of influenza prevention is strain-specific seasonal vaccination using inactivated viruses. Because influenza is subject to continuous antigenic drift, vaccines must be updated annually to match circulating viruses based on global surveillance data. Vaccine efficacy is difficult to predict and ranges widely from 10% to 60%, partially due to mismatches between vaccine and circulating viruses (35). In populations most susceptible to severe influenza disease, vaccine responses are suboptimal, and in some years, the vaccine offers no significant protection (6,7). Additionally, certain populations cannot be vaccinated due to contraindications Mouse monoclonal to PRKDC or forgo vaccination for personal or religious reasons (8,9). Apart from vaccines, small-molecule antiviral drugs, including oseltamivir, zanamivir, and baloxavir marboxil, have demonstrated efficacy for post-exposure prophylaxis of influenza if started soon after exposure to an index case. However, they are not appropriate for routine seasonal influenza prevention due to the potential for drugdrug interactions, short half-life, and the emergence of drug-resistant virus strains. Anti-influenza monoclonal antibodies (mAbs) are an emerging class of therapeutics with the potential to overcome the limitations of vaccines and antivirals. Multiple influenza proteins are possible targets neutralizing mAbs, including hemagglutinin (HA), neuraminidase (NA), and matrix protein 2. Among these, anti-HA antibodies have been extensively studied for their ability to block early phases of the virus lifecycle. HA protein consists of two functional domains: the globular head, which mediates virus attachment to host cell sialic acids, and the stem, which mediates HA maturation and endosomal fusion. Vaccine-elicited antibodies primarily target the.