Prevention Of Seasonal Influenza Research Articles

P-1104. Single-Dose and Repeat Single-Dose Ascending Dose Study Evaluating Safety, Tolerability, and Pharmacokinetics of Subcutaneous and Intramuscular CD388, a Novel Long-acting Drug-Fc Conjugate for Universal Prevention of Seasonal and Pandemic Influenza

Abstract Background CD388 is a novel antiviral drug-Fc conjugate (DFC) designed to deliver universal prevention of seasonal and pandemic influenza. Nonclinical studies have shown CD388 was effective prophylactically against a wide range of seasonal and pandemic influenza A and B strains in lethal and nonlethal mouse models of infection. Interim clinical pharmacokinetics (PK), indicating similar intramuscular (IM) and subcutaneous (SQ) exposures and long half-life (t1/2), and blinded safety results, indicating no safety concerns with CD388 or placebo, were presented last year (ID Week 2023), and final results are now available.Figure 1:Design of CD388 First in Human Study Methods The design of the CD388 First in Human study, conducted in healthy subjects is shown in Figure 1. CD388 for injection (100 mg/mL) was administered IM or SQ at doses of 50, 150, and 450, and 900 mg SQ only. Subjects in the 150 or 450 mg dose groups received a second single dose after a washout period of approximately 5 t1/2’s. Plasma CD388 concentrations and anti-CD388 antibody analysis were determined for subjects randomized to receive CD388 using validated methods. Safety was monitored throughout the study.Figure 2:Single Dose Mean +/- SD Plasma CD388 Concentrations Versus Time for CD388 Administered by Intramuscular Injection (Semi-logarithmic Scale) Results Pharmacokinetics of CD388 were similar following intramuscular or subcutaneous routes of administration. CD388 was absorbed rapidly and eliminated slowly with mean apparent half-life of elimination values ranging from ∼ 6 to 8 weeks (Figures 2 and 3). Increases in CD388 exposures were approximately dose proportional (Figure 4). Exposures were similar following a second single dose administration. Formation of anti-drug antibodies (ADA) were rare, at low titers when present, and did not affect PK. Most treatment emergent adverse events (TEAEs) were mild in intensity, and there were no deaths, or serious AEs. Overall, no dose-dependent trend was observed for TEAEs, and the proportion of participants that experienced at least 1 TEAE or drug-related TEAE was similar for both administration routes (IM and SQ).Figure 3:Single Dose Mean +/- SD Plasma CD388 Concentrations Versus Time for CD388 Administered by Subcutaneous Injection (Semi-logarithmic Scale) Conclusion CD388 absorption by both routes was rapid and elimination was slow, indicating that seasonal influenza prevention could be achieved with one dose per season. Lack of significant ADA formation with repeat administration supports annual use. No safety concerns were noted in this study.Figure 4:Single Dose Mean Plasma CD388 AUC for CD388 Administered by Intramuscular or Subcutaneous Injection Disclosures Shawn Flanagan, PhD, Cidara Therapeutics: Salaried Employee|Cidara Therapeutics: Employee|Cidara Therapeutics: Stocks/Bonds (Public Company)|Cidara Therapeutics: Stocks/Bonds (Public Company) Ozlem Equils, MD, Cidara Therapeutics: Employee|Cidara Therapeutics: Stocks/Bonds (Public Company) Roxana E. Rojas, M.D., Ph.D., Janssen Research & Development LLC: Employee|Janssen Research & Development LLC: Stocks/Bonds (Public Company)|Johnson and Johnson: Stocks/Bonds (Public Company) Tristan Baguet, PharmD, Johnson&johnson: Stocks/Bonds (Public Company) Sy-Shi Wang, Ph.D., Janssen Research & Development LLC: Employee|Janssen Research & Development LLC: Stocks/Bonds (Public Company) Voon Ong, Executive Director, Cidara Therapeutics: Stocks/Bonds (Public Company) Taylor Sandison, MD, MPH, Cidara Therapeutics Inc: Employee|Cidara Therapeutics Inc: Stocks/Bonds (Public Company)

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2024-25 Influenza Season.

This report updates the 2023-24 recommendations of the Advisory Committee on Immunization Practices (ACIP) concerning the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2022;72[No. RR-2]:1-24). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. Trivalent inactivated influenza vaccines (IIV3s), trivalent recombinant influenza vaccine (RIV3), and trivalent live attenuated influenza vaccine (LAIV3) are expected to be available. All persons should receive an age-appropriate influenza vaccine (i.e., one approved for their age), with the exception that solid organ transplant recipients aged 18 through 64 years who are receiving immunosuppressive medication regimens may receive either high-dose inactivated influenza vaccine (HD-IIV3) or adjuvanted inactivated influenza vaccine (aIIV3) as acceptable options (without a preference over other age-appropriate IIV3s or RIV3). Except for vaccination for adults aged ≥65 years, ACIP makes no preferential recommendation for a specific vaccine when more than one licensed and recommended vaccine is available. ACIP recommends that adults aged ≥65 years preferentially receive any one of the following higher dose or adjuvanted influenza vaccines: trivalent high-dose inactivated influenza vaccine (HD-IIV3), trivalent recombinant influenza vaccine (RIV3), or trivalent adjuvanted inactivated influenza vaccine (aIIV3). If none of these three vaccines is available at an opportunity for vaccine administration, then any other age-appropriate influenza vaccine should be used.Primary updates to this report include the following two topics: the composition of 2024-25 U.S. seasonal influenza vaccines and updated recommendations for vaccination of adult solid organ transplant recipients. First, following a period of no confirmed detections of wild-type influenza B/Yamagata lineage viruses in global surveillance since March 2020, 2024-25 U.S. influenza vaccines will not include an influenza B/Yamagata component. All influenza vaccines available in the United States during the 2024-25 season will be trivalent vaccines containing hemagglutinin derived from 1) an influenza A/Victoria/4897/2022 (H1N1)pdm09-like virus (for egg-based vaccines) or an influenza A/Wisconsin/67/2022 (H1N1)pdm09-like virus (for cell culture-based and recombinant vaccines); 2) an influenza A/Thailand/8/2022 (H3N2)-like virus (for egg-based vaccines) or an influenza A/Massachusetts/18/2022 (H3N2)-like virus (for cell culture-based and recombinant vaccines); and 3) an influenza B/Austria/1359417/2021 (Victoria lineage)-like virus. Second, recommendations for vaccination of adult solid organ transplant recipients have been updated to include HD-IIV3 and aIIV3 as acceptable options for solid organ transplant recipients aged 18 through 64 years who are receiving immunosuppressive medication regimens (without a preference over other age-appropriate IIV3s or RIV3).This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2024-25 influenza season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/acip-recs/hcp/vaccine-specific/flu.html?CDC_AAref_Val=https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines. Updates and other information are available from CDC's influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check this site periodically for additional information.

The economic and fiscal impact of incremental use of cell-based quadrivalent influenza vaccine for the prevention of seasonal influenza among healthcare workers in Italy

BackgroundSeasonal influenza has a significant impact on public health, generating substantial direct healthcare costs, production losses and fiscal effects. Understanding these consequences is crucial to effective decision-making and the development of preventive strategies. This study aimed to evaluate the economic and the fiscal impact of implementing an incremental strategy for seasonal influenza prevention using the cell-based quadrivalent influenza vaccine (QIVc) among healthcare workers (HCWs) in Italy.MethodsTo estimate the economic impact of implementing this strategy, we performed a cost analysis that considered direct healthcare costs, productivity losses and fiscal impact. The analysis considered a 3-year time horizon. A deterministic sensitivity analysis was also conducted.ResultsAssuming a vaccination coverage rate of 30% among HCWs, the analysis considered a total of 203 018 vaccinated subjects. On analysing the overall differential impact (including direct costs, indirect costs and fiscal impact), implementing QIVc vaccination as a preventative measure against influenza among HCWs in Italy would yield societal resource savings of €23 638.78 in the first year, €47 277.56 in the second year, and €70 916.35 in the third year, resulting in total resource savings of €141 832.69.ConclusionsThe study demonstrated that implementing the incremental use of QIVc as part of a preventive strategy for seasonal influenza among HCWs in Italy could yield positive economic outcomes, especially in terms of indirect costs and fiscal impact. The resources saved could be utilized to fund further public health interventions. Policy-makers should consider these findings when making decisions regarding influenza prevention strategies targeting HCWs.

2514. Single Ascending Dose Safety, Tolerability, and Pharmacokinetics of Subcutaneous and Intramuscular CD388, a Novel Long-acting Drug-Fc Conjugate for Universal Prevention of Seasonal and Pandemic Influenza

Abstract Background CD388 is a novel antiviral drug-Fc conjugate (DFC) designed to deliver universal prevention of seasonal and pandemic influenza. Nonclinical studies have shown CD388 was effective prophylactically against a wide range of seasonal and pandemic influenza A and B strains in lethal and nonlethal mouse models of infection. Methods The design of the ongoing blinded CD388 First in Human study, which is being conducted in healthy subjects is shown in Figure 1. CD388 for injection (100 mg/mL) was administered by intramuscular (IM) or subcutaneous (SQ) routes of administration. Single dose pharmacokinetics were determined for subjects in the 50 and 150 mg cohorts of each dosing route at protocol specified nominal time points; alias subject numbers were used to maintain blind. Plasma CD388 concentrations were determined for subjects randomized to receive CD388 using a validated hybrid immunoassay LC-MS method with lower limit of quantitation (LLOQ) of 0.1 µg/mL. Results CD388 appeared to be well absorbed by IM or SQ routes of administration with maximum plasma concentrations (Tmax) appearing from 2 to 13 days post dose, and quantifiable concentrations ( >LLOQ) lasting for several weeks to months (Figures 2 to 4). Mean apparent half-life of elimination was ∼ 50 days. Increases in CD388 exposures were approximately dose proportional for both routes (Figures 2 to 4). No dose limiting local or systemic safety concerns were noted from review of ongoing blinded safety data and the study is proceeding at doses higher than those reported herein. Conclusion Plasma concentrations of CD388, were similar following intramuscular or subcutaneous routes of administration and were sustained. No safety concerns have been noted in this ongoing study. Disclosures Shawn Flanagan, PhD, Cidara Therapeutics: Salaried Employee|Cidara Therapeutics: Stocks/Bonds Voon Ong, Executive Director, Cidara Therapeutics: Stocks/Bonds Tristan Baguet, PharmD, Johnson & Johnson: Employee Roxana E. Rojas, M.D., Ph.D., Janssen: Employee|Janssen: Stocks/Bonds Sy-Shi Wang, Ph.D., Janssen Pharmaceutical: Employee Ozlem Equils, MD, Cidara Therapeutics: Employee|Cidara Therapeutics: Stocks/Bonds

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023–24 Influenza Season

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023–24 Influenza Season

Mechanisms for the circulation of influenza A(H3N2) in China: A spatiotemporal modelling study.

Circulation of seasonal influenza is the product of complex interplay among multiple drivers, yet characterizing the underlying mechanism remains challenging. Leveraging the diverse seasonality of A(H3N2) virus and abundant climatic space across regions in China, we quantitatively investigated the relative importance of population susceptibility, climatic factors, and antigenic change on the dynamics of influenza A(H3N2) through an integrative modelling framework. Specifically, an absolute humidity driven multiscale transmission model was constructed for the 2013/2014, 2014/2015 and 2016/2017 influenza seasons that were dominated by influenza A(H3N2). We revealed the variable impact of absolute humidity on influenza transmission and differences in the occurring timing and magnitude of antigenic change for those three seasons. Overall, the initial population susceptibility, climatic factors, and antigenic change explained nearly 55% of variations in the dynamics of influenza A(H3N2). Specifically, the additional variation explained by the initial population susceptibility, climatic factors, and antigenic change were at 33%, 26%, and 48%, respectively. The vaccination program alone failed to fully eliminate the summer epidemics of influenza A(H3N2) and non-pharmacological interventions were needed to suppress the summer circulation. The quantitative understanding of the interplay among driving factors on the circulation of influenza A(H3N2) highlights the importance of simultaneous monitoring of fluctuations for related factors, which is crucial for precise and targeted prevention and control of seasonal influenza.

Transmission Patterns of Seasonal Influenza in China between 2010 and 2018.

Background Understanding the transmission source, pattern, and mechanism of infectious diseases is essential for targeted prevention and control. Though it has been studied for many years, the detailed transmission patterns and drivers for the seasonal influenza epidemics in China remain elusive. Methods In this study, utilizing a suite of epidemiological and genetic approaches, we analyzed the updated province-level weekly influenza surveillance, sequence, climate, and demographic data between 1 April 2010 and 31 March 2018 from continental China, to characterize detailed transmission patterns and explore the potential initiating region and drivers of the seasonal influenza epidemics in China. Results An annual cycle for influenza A(H1N1)pdm09 and B and a semi-annual cycle for influenza A(H3N2) were confirmed. Overall, the seasonal influenza A(H3N2) virus caused more infection in China and dominated the summer season in the south. The summer season epidemics in southern China were likely initiated in the “Lingnan” region, which includes the three most southern provinces of Hainan, Guangxi, and Guangdong. Additionally, the regions in the south play more important seeding roles in maintaining the circulation of seasonal influenza in China. Though intense human mobility plays a role in the province-level transmission of influenza epidemics on a temporal scale, climate factors drive the spread of influenza epidemics on both the spatial and temporal scales. Conclusion The surveillance of seasonal influenza in the south, especially the “Lingnan” region in the summer, should be strengthened. More broadly, both the socioeconomic and climate factors contribute to the transmission of seasonal influenza in China. The patterns and mechanisms revealed in this study shed light on the precise forecasting, prevention, and control of seasonal influenza in China and worldwide.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022-23 Influenza Season.

SummaryThis report updates the 2021–22 recommendations of the Advisory Committee on Immunization Practices (ACIP) concerning the use of seasonal influenza vaccines in the United States(MMWR Recomm Rep 2021;70[No. RR-5]:1–24). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. With the exception of vaccination for adults aged ≥65 years, ACIP makes no preferential recommendation for a specific vaccine when more than one licensed, recommended, and age-appropriate vaccine is available. All seasonal influenza vaccines expected to be available in the United States for the 2022–23 season are quadrivalent, containing hemagglutinin (HA) derived from one influenza A(H1N1)pdm09 virus, one influenza A(H3N2) virus, one influenza B/Victoria lineage virus, and one influenza B/Yamagata lineage virus. Inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4) are expected to be available. Trivalent influenza vaccines are no longer available, but data that involve these vaccines are included for reference.Influenza vaccines might be available as early as July or August, but for most persons who need only 1 dose of influenza vaccine for the season, vaccination should ideally be offered during September or October. However, vaccination should continue after October and throughout the season as long as influenza viruses are circulating and unexpired vaccine is available. For most adults (particularly adults aged ≥65 years) and for pregnant persons in the first or second trimester, vaccination during July and August should be avoided unless there is concern that vaccination later in the season might not be possible. Certain children aged 6 months through 8 years need 2 doses; these children should receive the first dose as soon as possible after vaccine is available, including during July and August. Vaccination during July and August can be considered for children of any age who need only 1 dose for the season and for pregnant persons who are in the third trimester if vaccine is available during those monthsUpdates described in this report reflect discussions during public meetings of ACIP that were held on October 20, 2021; January 12, 2022; February 23, 2022; and June 22, 2022. Primary updates to this report include the following three topics: 1) the composition of 2022–23 U.S. seasonal influenza vaccines; 2) updates to the description of influenza vaccines expected to be available for the 2022–23 season, including one influenza vaccine labeling change that occurred after the publication of the 2021–22 ACIP influenza recommendations; and 3) updates to the recommendations concerning vaccination of adults aged ≥65 years. First, the composition of 2022–23 U.S. influenza vaccines includes updates to the influenza A(H3N2) and influenza B/Victoria lineage components. U.S.-licensed influenza vaccines will contain HA derived from an influenza A/Victoria/2570/2019 (H1N1)pdm09-like virus (for egg-based vaccines) or an influenza A/Wisconsin/588/2019 (H1N1)pdm09-like virus (for cell culture–based or recombinant vaccines); an influenza A/Darwin/9/2021 (H3N2)-like virus (for egg-based vaccines) or an influenza A/Darwin/6/2021 (H3N2)-like virus (for cell culture–based or recombinant vaccines); an influenza B/Austria/1359417/2021 (Victoria lineage)-like virus; and an influenza B/Phuket/3073/2013 (Yamagata lineage)-like virus. Second, the approved age indication for the cell culture–based inactivated influenza vaccine, Flucelvax Quadrivalent (ccIIV4), was changed in October 2021 from ≥2 years to ≥6 months. Third, recommendations for vaccination of adults aged ≥65 years have been modified. ACIP recommends that adults aged ≥65 years preferentially receive any one of the following higher dose or adjuvanted influenza vaccines: quadrivalent high-dose inactivated influenza vaccine (HD-IIV4), quadrivalent recombinant influenza vaccine (RIV4), or quadrivalent adjuvanted inactivated influenza vaccine (aIIV4). If none of these three vaccines is available at an opportunity for vaccine administration, then any other age-appropriate influenza vaccine should be usedThis report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2022–23 influenza season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html . These recommendations apply to U.S.-licensed influenza vaccines used according to Food and Drug Administration–licensed indications. Updates and other information are available from CDC’s influenza website ( https://www.cdc.gov/flu ). Vaccination and health care providers should check this site periodically for additional information.

Adverse Events of Interest Following Influenza Vaccination in the First Season of Adjuvanted Trivalent Immunization: Retrospective Cohort Study.

BackgroundVaccination is the most effective form of prevention of seasonal influenza; the United Kingdom has a national influenza vaccination program to cover targeted population groups. Influenza vaccines are known to be associated with some common minor adverse events of interest (AEIs), but it is not known if the adjuvanted trivalent influenza vaccine (aTIV), first offered in the 2018/2019 season, would be associated with more AEIs than other types of vaccines.ObjectiveWe aim to compare the incidence of AEIs associated with different types of seasonal influenza vaccines offered in the 2018/2019 season.MethodsWe carried out a retrospective cohort study using computerized medical record data from the Royal College of General Practitioners Research and Surveillance Centre sentinel network database. We extracted data on vaccine exposure and consultations for European Medicines Agency–specified AEIs for the 2018/2019 influenza season. We used a self-controlled case series design; computed relative incidence (RI) of AEIs following vaccination; and compared the incidence of AEIs associated with aTIV, the quadrivalent influenza vaccine, and the live attenuated influenza vaccine. We also compared the incidence of AEIs for vaccinations that took place in a practice with those that took place elsewhere.ResultsA total of 1,024,160 individuals received a seasonal influenza vaccine, of which 165,723 individuals reported a total of 283,355 compatible symptoms in the 2018/2019 season. Most AEIs occurred within 7 days following vaccination, with a seasonal effect observed. Using aTIV as the reference group, the quadrivalent influenza vaccine was associated with a higher incidence of AEIs (RI 1.46, 95% CI 1.41-1.52), whereas the live attenuated influenza vaccine was associated with a lower incidence of AEIs (RI 0.79, 95% CI 0.73-0.83). No effect of vaccination setting on the incidence of AEIs was observed.ConclusionsRoutine sentinel network data offer an opportunity to make comparisons between safety profiles of different vaccines. Evidence that supports the safety of newer types of vaccines may be reassuring for patients and could help improve uptake in the future.

Technical guidelines for seasonal influenza vaccination in China (2021-2022)

Technical guidelines for seasonal influenza vaccination in China (2021-2022)

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season.

Clinical efficacy and safety of high dose trivalent influenza vaccine in adults and immunosuppressed populations – A systematic review and meta-analysis

ObjectivesInfluenza is associated with significant morbidity and mortality, especially in older and immunocompromised patients. Few data are available on the clinical benefit of high dose trivalent influenza vaccine (TIV). We aimed to assess the clinical efficacy and safety of high dose TIV. MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), evaluating high dose versus standard dose TIV for prevention of seasonal influenza in adult population. Primary outcome was laboratory-confirmed influenza. Subgroups analyses included older adults and immunocompromised patients. ResultsWe included 16 trials, 47,857 patients; 10 included older adults and three immunocompromised patients. Laboratory confirmed influenza was significantly reduced with high dose TIV (relative risk 0.76, 95% confidence interval 0.64 to 0.9). This outcome stemmed mainly from one trial in older adults. Specifically, A(H3N2) laboratory confirmed influenza, but not A(H1N1) or B lineages, was reduced. No difference in mortality or hospitalizations was demonstrated. Immunological response was significantly higher with high dose vaccine. Serious adverse events were significantly less common in the high dose group. ConclusionsHigh dose TIV lowers the rates of laboratory confirmed influenza, mainly A (H3N2), in older adults vs. standard dose. Further studies should address immunocompromised patients and report clinical outcomes.

Seasonal influenza during pregnancy

Seasonal Influenza is an acute respiratory illness caused by Influenza A or B viruses. Its presentation is commonly with signs and symptoms of upper respiratory tract involvement such as cough, sore throat and runny nose, associated with generalized systemic symptoms such as fever, headaches, myalgia, and weakness. The severity of symptoms is very variable, ranging from mild self-limiting infection to severe acute respiratory illness requiring intensive interventions. It usually occurs during the winter season and can lead to outbreaks and epidemics worldwide. Influenza is associated with increased morbidity and mortality in high-risk populations including pregnant women and up to two weeks postpartum. Rapid and accurate diagnosis of Influenza is necessary for prompt treatment to reduce morbidity. General public health measures and vaccination are recommended to reduce morbidity and control the spread of the disease. There are many published articles on the several Influenza epidemics that have occurred in this century. In this article, we aim to review the epidemiology, clinical manifestations, diagnosis, treatment, and prevention of seasonal Influenza during pregnancy. We performed an electronic search on PubMed, Cochrane database, National guidelines clearing house and Google Scholar databases.

1276. Evaluation of CD377, a Novel Antiviral Fc-Conjugate (AVC), In Vitro Activity and In Vivo Efficacy in Immune-Competent and -Deficient (SCID) Lethal Mouse Models

BackgroundCidara’s AVCs are novel, potent, antiviral agents conjugated with the Fc domain of human IgG1. CD377 is an AVC development candidate being evaluated for prevention and treatment of seasonal and pandemic influenza, including in immune-deficient populations unable to benefit from vaccination. We evaluated CD377 in vitro and in SCID mice to determine the impact of compromised immune status on efficacy.MethodsCD377 and comparators (oseltamivir [OS], zanamivir [ZA], baloxavir marboxil [BM]) were evaluated in vitro by neuraminidase inhibition (NAI), and cytopathic effect (CPE) assays. The pharmacokinetics (PK) and efficacy of CD377 were determined in immune-competent (IC; BALB/c) and immune-deficient (ID; BALB/c SCID) mice. Efficacy was assessed by intranasal challenge at 3x the LD95 of influenza A/Puerto Rico/8/1934 (H1N1), followed by a single subcutaneous (SC) dose of CD377, 2 hours post-challenge. The SCID study also evaluated the efficacy of BM at 3 mg/kg (BID x 1 day). Body weights (BW) were monitored for 21 days, with 20% BW loss recorded as mortality.ResultsIn vitro evaluation by NAI showed CD377, OS, and ZA to be approximately equipotent, with IC50 values between 0.5 and 1.7 nM. However, by CPE, CD377 was ~4.5-fold more active than BM and >1,000-fold more active than OS and ZA.In vivo, the PK of CD377 was found to be comparable in IC and ID mice. In subsequent efficacy studies, CD377 was protective at 0.1 mg/kg in IC mice (P=0.0020 vs. vehicle), while control groups fully succumbed to infection by Day 7 (Fig. 1A).In a similar study with ID mice, CD377 dosed at 0.1 mg/kg was also fully protective (P=0.0020). In contrast, mice treated with 6 mg/kg (total dose) of BM were only partially protected until day 13 (40% mortality by study end) (Fig. 1B). The potency of CD377 was further supported by BW data, which mirrored the survival data in both studies.ConclusionCD377 exhibited potent in vitro activity and had similar PK in IC and ID mice. In efficacy studies, CD377 demonstrated robust potency in both IC and ID mouse models at equivalent doses (0.1 mg/kg, SC, single dose). These results support further development of CD377 as a novel antiviral for the prevention and treatment of influenza infection, including in people with immune deficiencies and higher risk of infection.Balb/c and Balb/c SCID DisclosuresJames Levin, PhD, Cidara Therapeutics (Shareholder) Karin Amundson, B.S., Cidara Therapeutics (Shareholder) Allen Borchardt, PhD, Cidara Therapeutics (Employee) Thanh Lam, PhD, Cidara Therapeutics (Shareholder) Tom Brady, PhD, Cidara Therapeutics (Shareholder) Elizabeth Abelovski, B.S., Cidara Therapeutics (Shareholder) Simon Döhrmann, PhD, Cidara Therapeutics (Shareholder) Jason Cole, PhD, Cidara Therapeutics (Shareholder) Voon Ong, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Les Tari, PhD, Cidara Therapeutics (Shareholder)

Promotion of the influenza vaccination to hospital staff during pre-employment health check: a prospective, randomised, controlled trial

BackgroundVaccination is the most effective prevention of seasonal influenza. Despite its recommendation and active promotion, vaccination coverage remains low among healthcare staff. The goal of the study was to test if a pre-employment health check is a good opportunity to promote future vaccination against influenza among healthcare workers newly hired by a university hospital.MethodsAll new hospital employees active at the bedside who underwent a pre-employment health check between the end of 2016’s influenza epidemic and the start of the next influenza vaccination campaign were randomly allocated to a control group or an intervention group. The intervention consisted of a semi-structured dialog and the release of an information leaflet about influenza and influenza vaccination during the check-up, and the shipment of a postcard reminder 2 weeks before the next vaccination campaign. Vaccination rates during the campaign were compared among the two groups.ResultsThree hundred fifty-seven employees were included. Vaccination rates were similar in both groups: 79/172 (46%) in the control and 92/185 (50%) in the intervention group. A significantly higher rate of vaccination was noted among physicians (70/117, 60%) than among other employees (101/240, 42%, p = 0.001). In a pre-defined exploratory analysis among physicians, the vaccination rate was higher in the intervention group (36/51, 71%) than in the control group (34/65, 52%, p = 0.046).ConclusionsPromotion of the influenza vaccine during pre-employment health check did not improve the vaccination rate of newly hired hospital healthcare workers overall during the next influenza vaccination campaign. Results suggest a favourable impact on the vaccination rate of physicians. Thus, there may be an interest in using communication strategies tailored to the different categories of healthcare workers to promote the influenza vaccine during pre-employment health check.Trial registrationClinicalTrials, NCT02758145. Registered 26 April 2016.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2020-21 Influenza Season.

SummaryThis report updates the 2019–20 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2019;68[No. RR-3]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. Inactivated influenza vaccines (IIVs), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4) are expected to be available. Most influenza vaccines available for the 2020–21 season will be quadrivalent, with the exception of MF59-adjuvanted IIV, which is expected to be available in both quadrivalent and trivalent formulations.Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 23, 2019; February 26, 2020; and June 24, 2020. Primary updates to this report include the following two items. First, the composition of 2020–21 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Victoria lineage components. Second, recent licensures of two new influenza vaccines, Fluzone High-Dose Quadrivalent and Fluad Quadrivalent, are discussed. Both new vaccines are licensed for persons aged ≥65 years. Additional changes include updated discussion of contraindications and precautions to influenza vaccination and the accompanying Table, updated discussion concerning use of LAIV4 in the setting of influenza antiviral medication use, and updated recommendations concerning vaccination of persons with egg allergy who receive either cell culture–based IIV4 (ccIIV4) or RIV4.The 2020–21 influenza season will coincide with the continued or recurrent circulation of SARS-CoV-2 (the novel coronavirus associated with coronavirus disease 2019 [COVID-19]). Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient illnesses, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html.This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2020–21 season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used within Food and Drug Administration (FDA)–licensed indications. Updates and other information are available from CDC’s influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check this site periodically for additional information.

Meta-analysis on effectiveness of live attenuated influenza vaccine against seasonal influenza in children

Objective: To evaluate the effectiveness of live attenuated influenza vaccine (LAIV) in the prevention of seasonal influenza in children aged 2-17 years. Methods: Literature retrieval of case-control studies on the effectiveness of LAIV against seasonal influenza in children published from January 2003 to November 2018 was conducted through Web of Science, PubMed, and ScienceDirect databases. The Stata 13.1 software was used for Meta-analysis. Results: A total of 14 studies were included in this study, and all were test-negative design (TND) studies. Our Meta-analysis showed that the effectiveness of LAIV in children was 49% (95%CI: 40%-57%). Subgroup analysis found that the protection rate of LAIV was 35% against influenza A (H1N1) pdm09 (95%CI: 5%-56%), 35% against influenza A (H3N2) (95%CI: 21%-46%), and 71% against influenza B (95%CI: 55%-82%). The protection rates of trivalent LAIV and quadrivalent LAIV in children were 56% (95%CI: 48%-63%) and 44% (95%CI: 27%-57%), respectively. The protection rates of LAIV in Europe and North America were 65% (95%CI: 47%-77%) and 46% (95%CI: 36%-55%), respectively. Conclusion: LAIV has a certain preventive effect on seasonal influenza in children aged 2-17 years.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2019-20 Influenza Season.

SummaryThis report updates the 2018–19 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2018;67[No. RR-3]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. A licensed, recommended, and age-appropriate vaccine should be used. Inactivated influenza vaccines (IIVs), recombinant influenza vaccine (RIV), and live attenuated influenza vaccine (LAIV) are expected to be available for the 2019–20 season. Standard-dose, unadjuvanted, inactivated influenza vaccines will be available in quadrivalent formulations (IIV4s). High-dose (HD-IIV3) and adjuvanted (aIIV3) inactivated influenza vaccines will be available in trivalent formulations. Recombinant (RIV4) and live attenuated influenza vaccine (LAIV4) will be available in quadrivalent formulations.Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 25, 2018; February 27, 2019; and June 27, 2019. Primary updates in this report include the following two items. First, 2019–20 U.S. trivalent influenza vaccines will contain hemagglutinin (HA) derived from an A/Brisbane/02/2018 (H1N1)pdm09–like virus, an A/Kansas/14/2017 (H3N2)–like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent influenza vaccines will contain HA derived from these three viruses, and a B/Phuket/3073/2013–like virus (Yamagata lineage). Second, recent labeling changes for two IIV4s, Afluria Quadrivalent and Fluzone Quadrivalent, are discussed. The age indication for Afluria Quadrivalent has been expanded from ≥5 years to ≥6 months. The dose volume for Afluria Quadrivalent is 0.25 mL for children aged 6 through 35 months and 0.5 mL for all persons aged ≥36 months (≥3 years). The dose volume for Fluzone Quadrivalent for children aged 6 through 35 months, which was previously 0.25 mL, is now either 0.25 mL or 0.5 mL. The dose volume for Fluzone Quadrivalent is 0.5 mL for all persons aged ≥36 months (≥3 years).This report focuses on the recommendations for use of vaccines for the prevention and control of influenza during the 2019–20 season in the United States. A brief summary of these recommendations and a Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used within Food and Drug Administration–licensed indications. Updates and other information are available from CDC’s influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check this site periodically for additional information.

Cumulative clinical experience with MF59-adjuvanted trivalent seasonal influenza vaccine in young children

ObjectiveTo demonstrate the potential of an MF59-adjuvanted inactivated trivalent seasonal influenza vaccine (aIIV3; Fluad™) to improve the immune response in young children, we review the immunogenicity, efficacy, and safety/tolerability of aIIV3 from a comprehensive clinical development program in a pediatric population with a specific need for improved influenza vaccines. MethodsData were analyzed from a series of 1 phase Ib, 3 phase II, and 2 phase III studies involving 11,942 children aged 6 months through 5years. ResultsThe clinical data showed that aIIV3 had statistically significantly greater immunogenicity and efficacy in the prevention of influenza compared to conventional inactivated trivalent seasonal influenza vaccines (IIV3s). The safety profile of aIIV3 was generally similar to that of nonadjuvanted IIV3, apart from an increased frequency of solicited adverse events (AEs) following vaccination. The majority of solicited AEs were mild or moderate in severity and resolved within 1 to 3 days. ConclusionsaIIV3 was well tolerated, with immunogenicity and efficacy exceeding that of conventional IIV3 in children 6 months through 5years of age. The MF59-adjuvanted vaccine has the potential to fulfill an unmet clinical need in the prevention of seasonal influenza in this age group.

MMWR: Prevention and control of seasonal influenza

MMWR: Prevention and control of seasonal influenza