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Several vaccines are approved in the United States for seasonal influenza vaccination every year. Here we compare the impact of repeat influenza vaccination on hemagglutination inhibition (HI) titers, antibody binding and affinity maturation to individual hemagglutinin (HA) domains, HA1 and HA2, across vaccine platforms. Fold change in HI and antibody binding to HA1 trends higher for H1N1pdm09 and H3N2 but not against B strains in groups vaccinated with FluBlok compared with FluCelvax and Fluzone. Antibody-affinity maturation occurs against HA1 domain of H1N1pdm09, H3N2 and B following vaccination with all vaccine platforms, but not against H1N1pdm09-HA2. Importantly, prior year vaccination of subjects receiving repeat vaccinations demonstrated reduced antibody-affinity maturation to HA1 of all three influenza virus strains irrespective of the vaccine platform. This study identifies an important impact of repeat vaccination on antibody-affinity maturation following vaccination, which may contribute to lower vaccine effectiveness of seasonal influenza vaccines in humans Here, Khurana et al. report the results of a phase 4 clinical trial with three FDA approved influenza vaccines and show that repeat influenza vaccination results in reduced antibody affinity maturation to hemagglutinin domain 1 irrespective of vaccine platform.

\"Pandemics, Science and Policy examines the case study of the World Health Organisation's (WHO) representation and management of the 2009 H1N1 Pandemic. It analyses key criticisms made about the WHO's actions through an examination of the social context in which pandemic management decisions were made, and ultimately illustrations the various ways in which the WHO's account was vulnerable to contestation.Abeysinghe provides a persuasive account of the interplay between uncertain science and the creation of global policy. The book demonstrates that the fragility of the WHO's account and decisions largely lay in both the (lack of) scientific evidence the WHO received, and its use and representation of this evidence. Importantly, it shows how uncertain risks can affect policy and action on the global level\"--Provided by publisher.

In a multinational trial in children, a quadrivalent influenza vaccine (with both Victoria and Yamagata influenza B lineages, only one of which is included in the current trivalent vaccine) had about 59% efficacy. The incidence of influenza among children is high, and the illness is associated with substantial increases in outpatient visits and hospitalizations during the influenza season. 1 – 4 Routine vaccination of children against influenza is recommended in the United States 5 and some other countries, despite limited evidence of the efficacy of inactivated influenza vaccine from randomized, controlled trials involving children. 6 When trivalent influenza vaccines (TIVs) are used, there is a possibility of a mismatch between circulating and vaccine B strains, which results in inadequate protection from the vaccine. 7 – 10 A quadrivalent vaccine containing both B lineages would eliminate B-lineage mismatch. This may . . .

In this randomized trial conducted over the 2019–2024 influenza seasons, baloxavir resulted in a significantly lower incidence of transmission of influenza virus from patients to household contacts than placebo.

High-dose inactivated influenza vaccine has been shown to provide protection against influenza that is superior to that with the standard dose. However, data from individually randomized trials on the effectiveness of the high-dose vaccine against severe outcomes are limited. In this pragmatic, open-label, randomized, controlled trial conducted in Denmark during the 2022-2023, 2023-2024, and 2024-2025 influenza seasons, we assigned older adults (≥65 years of age) to receive the high dose of the inactivated influenza vaccine or the standard dose. Data collection relied on nationwide administrative health registries. The primary end point was hospitalization for influenza or pneumonia that occurred from 14 days after vaccination through May 31 of the following year. Of the 332,438 participants who underwent randomization, 166,218 were assigned to receive the high-dose vaccine and 166,220 to receive the standard-dose vaccine. The mean (±SD) age of the participants was 73.7±5.8 years, and 161,538 participants (48.6%) were women. A primary end-point event occurred in 1138 participants (0.68%) in the high-dose group and in 1210 (0.73%) in the standard-dose group (relative vaccine effectiveness, 5.9%; 95.2% confidence interval [CI], -2.1 to 13.4; P = 0.14). Hospitalization for influenza occurred in 0.06% of the participants in the high-dose group and in 0.11% of those in the standard-dose group (relative vaccine effectiveness, 43.6%; 95.2% CI, 27.5 to 56.3); hospitalization for pneumonia occurred in 0.63% and 0.63%, respectively (relative effectiveness, 0.5%; 95.2% CI, -8.6 to 8.8); hospitalization for cardiorespiratory disease in 2.25% and 2.38% (relative effectiveness, 5.7%; 95.2% CI, 1.4 to 9.9); hospitalization for any cause in 9.38% and 9.58% (relative effectiveness, 2.1%; 95.2% CI, -0.1 to 4.3), and death from any cause in 0.67% and 0.66% (relative effectiveness, -2.5%; 95.2% CI, -11.6 to 5.9). The incidence of serious adverse events was similar in the two groups. In this trial, a high-dose inactivated influenza vaccine did not result in a significantly lower incidence of hospitalization for influenza or pneumonia than a standard dose among older adults. (Funded by Sanofi; DANFLU-2 ClinicalTrials.gov number, NCT05517174; EU Clinical Trials Register number, 2022-500657-17-00.).

In adults 65 to 79 years of age, there appeared to be fewer hospitalizations for influenza or pneumonia with high-dose influenza vaccine than with the standard dose, with a similar incidence of serious adverse events.

Influenza viruses cause substantial annual morbidity and mortality globally. Current vaccines protect against influenza only when well matched to the circulating strains. However, antigenic drift can cause considerable mismatches between vaccine and circulating strains, substantially reducing vaccine effectiveness. Moreover, current seasonal vaccines are ineffective against pandemic influenza, and production of a vaccine matched to a newly emerging virus strain takes months. Therefore, there is an unmet medical need for a broadly protective influenza virus vaccine. We aimed to test the ability of chimeric H1 haemagglutinin-based universal influenza virus vaccine candidates to induce broadly cross-reactive antibodies targeting the stalk domain of group 1 haemagglutinin-expressing influenza viruses. We did a randomised, observer-blinded, phase 1 study in healthy adults in two centres in the USA. Participants were randomly assigned to one of three prime–boost, chimeric haemagglutinin-based vaccine regimens or one of two placebo groups. The vaccine regimens included a chimeric H8/1, intranasal, live-attenuated vaccine on day 1 followed by a non-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine on day 85; the same regimen but with the inactivated vaccine being adjuvanted with AS03; and an AS03-adjuvanted, chimeric H8/1, intramuscular, inactivated vaccine followed by an AS03-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine. In this planned interim analysis, the primary endpoints of reactogenicity and safety were assessed by blinded study group. We also assessed anti-H1 haemagglutinin stalk, anti-H2, anti-H9, and anti-H18 IgG antibody titres and plasmablast and memory B-cell responses in peripheral blood. This trial is registered with ClinicalTrials.gov, number NCT03300050. Between Oct 10, 2017, and Nov 27, 2017, 65 participants were enrolled and randomly assigned. The adjuvanted inactivated vaccine, but not the live-attenuated vaccine, induced a substantial serum IgG antibody response after the prime immunisation, with a seven times increase in anti-H1 stalk antibody titres on day 29. After boost immunisation, all vaccine regimens induced detectable anti-H1 stalk antibody (2·2–5·6 times induction over baseline), cross-reactive serum IgG antibody, and peripheral blood plasmablast responses. An unsolicited adverse event was reported for 29 (48%) of 61 participants. Solicited local adverse events were reported in 12 (48%) of 25 participants following prime vaccination with intramuscular study product or placebo, in 12 (33%) of 36 after prime immunisation with intranasal study product or placebo, and in 18 (32%) of 56 following booster doses of study product or placebo. Solicited systemic adverse events were reported in 14 (56%) of 25 after prime immunisation with intramuscular study product or placebo, in 22 (61%) of 36 after immunisation with intranasal study product or placebo, and in 21 (38%) of 56 after booster doses of study product or placebo. Disaggregated safety data were not available at the time of this interim analysis. The tested chimeric haemagglutinin-based, universal influenza virus vaccine regimens elicited cross-reactive serum IgG antibodies that targeted the conserved haemagglutinin stalk domain. This is the first proof-of-principle study to show that high anti-stalk titres can be induced by a rationally designed vaccine in humans and opens up avenues for further development of universal influenza virus vaccines. On the basis of the blinded study group, the vaccine regimens were tolerable and no safety concerns were observed. Bill & Melinda Gates Foundation.

In a randomized, double-blind trial that treated household contacts of patients with influenza with a single dose of baloxavir or placebo, participants taking baloxavir had a lower risk of influenza (1.9%) than placebo controls (13.6%). Adverse events were similar in the two groups.