Cytokine Biomarkers of Exacerbations in Sputum From Patients With Chronic Obstructive Pulmonary Disease: A Prospective Cohort Study.

Background: We determined the relationships between cytokine expression in sputum and clinical data to characterize and understand chronic obstructive pulmonary disease (COPD) exacerbations in people with COPD.

Methods: We measured 30 cytokines in 936 sputum samples, collected at stable state and exacerbation visits from 99 participants in the Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) study (ClinicalTrials.gov NCT01360398).

Systems analysis of human responses to an aluminium hydroxide-adsorbed TLR7 agonist (AS37) adjuvanted vaccine reveals a dose-dependent and specific activation of the interferon-mediated antiviral response.

The candidate Adjuvant System AS37 contains a synthetic toll-like receptor agonist (TLR7a) adsorbed to alum. In a phase I study (NCT02639351), healthy adults were randomised to receive one dose of licensed alum-adjuvanted meningococcal serogroup C (MenC-CRM) conjugate vaccine (control) or MenC-CRM conjugate vaccine adjuvanted with AS37 (TLR7a dose 12.5, 25, 50 or 100 µg).

The droplet size of emulsion adjuvants has significant impact on their potency, due to differences in immune cell-recruitment and -activation.

Self-emulsification is routinely used for oral delivery of lipophilic drugs in vivo, with the emulsion forming in vivo. We modified this technique to prepare novel oil-in-water emulsions of varying droplet size and composition on bench to enable adjuvanted vaccine delivery. We used these formulations to show that smaller droplets (20 nm) were much less effective as adjuvants for an influenza vaccine in mice than the emulsion droplet size of commercial influenza vaccine adjuvants (~160 nm).

Mannosylation of LNP Results in Improved Potency for Self-Amplifying RNA (SAM) Vaccines.

Mannosylation of Lipid Nanoparticles (LNP) can potentially enhance uptake by Antigen Presenting Cells, which are highly abundant in dermal tissues, to improve the potency of Self Amplifying mRNA (SAM) vaccines in comparison to the established unmodified LNP delivery system. In the current studies, we evaluated mannosylated LNP (MLNP), which were obtained by incorporation of a stable Mannose-cholesterol amine conjugate, for the delivery of an influenza (hemagglutinin) encoded SAM vaccine in mice, by both intramuscular and intradermal routes of administration. SAM MLNP exhibited enhanced uptake in comparison to unglycosylated LNP from bone marrow-derived dendritic cells, and more rapid onset of the antibody response, independent of the route.

Co-administration of GM-CSF expressing RNA is a powerful tool to enhance potency of SAM-based vaccines.

Self-amplifying mRNAs (SAM)-based vaccines have been shown to induce a robust immune response in various animal species against both viral and bacterial pathogens. Due to their synthetic nature and to the versatility of the manufacturing process, SAM technology may represent an attractive solution for rapidly producing novel vaccines, which is particularly critical in case of pandemic infections or diseases mediated by newly emerging pathogens. Recent published data support the hypothesis that Antigen Presenting Cells (APCs) are responsible for CD8+ T-cell priming after SAM vaccination, suggesting cross-priming as the key mechanism for antigen presentation by SAM vaccines.

Positive Contribution of Adjuvanted Influenza Vaccines to the Resolution of Bacterial Superinfections.

Background: Most preclinical studies assess vaccine effectiveness in single-pathogen infection models. This is unrealistic given that humans are continuously exposed to different commensals and pathogens in sequential and mixed infections. Accordingly, complications from secondary bacterial infection are a leading cause of influenza-associated morbidity and mortality.

Sublingual immunization with a subunit influenza vaccine elicits comparable systemic immune response as intramuscular immunization, but also induces local IgA and TH17 responses.

Influenza is a vaccine-preventable disease that remains a major health problem world-wide. Needle and syringe are still the primary delivery devices, and injection of liquid vaccine into the muscle is still the primary route of immunization. Vaccines could be more convenient and effective if they were delivered by the mucosal route.

The adjuvant MF59 induces ATP release from muscle that potentiates response to vaccination.

Vaccines are the most effective agents to control infections. In addition to the pathogen antigens, vaccines contain adjuvants that are used to enhance protective immune responses. However, the molecular mechanism of action of most adjuvants is ill-known, and a better understanding of adjuvanticity is needed to develop improved adjuvants based on molecular targets that further enhance vaccine efficacy.

The adjuvant effect of MF59 is due to the oil-in-water emulsion formulation, none of the individual components induce a comparable adjuvant effect.

MF59 is a safe and effective vaccine adjuvant that has been used in a licensed seasonal influenza vaccine for 15 years. The purpose of the present studies was to directly address a question that has been asked of us on many occasions: "which is the adjuvant active component of MF59?". Since we have recently gained a number of insights on how MF59 works as an adjuvant, we were able to use these approaches to evaluate if the individual components of MF59 (squalene oil, the surfactants Span 85 and Tween 80 or the citrate buffer) showed any direct immunostimulatory activity.