Influenza vaccine effectiveness varies annually due to the fast evolving seasonal influenza A(H3N2) strain and egg-derived mutations-both of which can cause a mismatch between the vaccine and circulating strains. To address these limitations, we have developed a hemagglutinin (HA)-based protein-detergent nanoparticle influenza vaccine (NIV) with a saponin-based Matrix-M™ adjuvant. In a phase 1 clinical trial of older adults, the vaccine demonstrated broadly cross-reactive A(H3N2) HA antibody responses. Two broadly neutralizing monoclonal antibodies derived from NIV-immunized mice were characterized by transmission electron microscopy (TEM), antibody competition assays, fluorescence-activated cell sorting (FACS) analysis, and protein-protein docking. These antibodies recognize two conserved regions of the head domain, namely the receptor binding site and the vestigial esterase subdomain, thus demonstrating the potential for an HA subunit vaccine to elicit antibodies targeting structurally and antigenically distinct but conserved sites. Antibody competition studies with sera from the phase 1 trial in older adults confirmed that humans also make antibodies to these two head domains and against the highly conserved stem domain. This data supports the potential of an adjuvanted recombinant HA nanoparticle vaccine to induce broadly protective immunity and improved vaccine efficacy.
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http://dx.doi.org/10.3390/vaccines8010099 | DOI Listing |
Alzheimers Dement
December 2024
University of Florida / Center for Translational Research in Neurodegenerative Disease, Gainesville, FL, USA.
Background: Vaxxinity is developing an active immunotherapy targeting Tau for Alzheimer's disease (AD) and other tauopathies. VXX-301 is a multi-epitope vaccine designed to target the N-terminal and repeat domains of Tau. This design enables targeting multiple forms of Tau thought to contribute to Tau associated pathologies.
View Article and Find Full Text PDFBackground: The key advantage of active immunization is the induction of sustained, polyclonal antibody responses that are readily boosted by occasional immunizations. Recent clinical trial outcomes for monoclonal antibodies lecanemab and donanemab, establish the relevance of targeting pathological Abeta for clearing amyloid plaques in Alzheimer's disease. ACI-24.
View Article and Find Full Text PDFBackground: A large body of evidence now indicates that the most pathogenic species of Aß in Alzheimer's disease (AD) consist of soluble toxic oligomers (AßO) as opposed to insoluble fibrils and monomers. Using our computational platform, we identified 4 different AßO-restricted conformational B cell epitopes (300, 301, 303, 305) that were tested as vaccines for their ability to induce an antibody response that selectively targets toxic AßO, without inducing potentially detrimental B or T cell responses against plaque or normal Aß. A novel ex vivo approach was then used to select an optimal vaccine configuration amongst the 15 possible combinations of the 4 epitopes to provide maximal binding to a toxic oligomer-enriched low molecular weight (LMW) fraction of soluble AD brain extracts.
View Article and Find Full Text PDFJBI Evid Synth
January 2025
LLUH Center for Evidence Synthesis, Loma Linda University Health, Loma Linda, California, USA.
Objective: The objective of the systematic review will be to evaluate the effect of paternity leave or fathers' parental leave on infant mortality rate, hospitalization, vaccination compliance, and breastfeeding duration.
Introduction: Current studies indicate that paternity leave positively affects infant health, but there is a significant lack of synthesized research on its impact on key infant health indicators. A systematic review of the existing evidence will help identify best practices and guide further research and policy development in this area.
Cannabis
December 2024
Firestone Institute for Respiratory Health - Division of Respirology, Department of Medicine, McMaster University.
Objective: The potential impact of cigarette and cannabis smoking on COVID-19 infection outcomes is not well understood. We investigated the association between combustible tobacco use and dried cannabis use with COVID-19 infection in a longitudinal cohort of community adults.
Method: The sample comprised 1,343 participants, originally enrolled in 2018, who reported their cigarette and cannabis use in 11 assessments over 44 months, until 2022.
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