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At least 19 recordsLinked to original sources
PubMed2026

Whole cell inactivated poly-bacterial preparation MV130 effect on nasal mucosal immunity and experimental human pneumococcal carriage: double-blind randomised controlled trial with controlled human infection model.

BACKGROUND: Bacterial mucosal immunotherapy has shown protection of children and adults from both viral and bacterial respiratory infections, offering the potential to reduce antimicrobial use, and hence also control antimicrobial resistance (AMR). Pneumococcal carriage of vaccine type Streptococcus pneumoniae remains high in Malawi despite infant conjugate vaccination and AMR is increasing. We compared nasal inflammation following sublingual bacterial immunotherapy including S. pneumoniae (MV130, Inmunotek, Spain) or placebo and determined the effect in an experimental human pneumococcal carriage model. METHODS: A double-blind, randomised, placebo-controlled trial in healthy adult volunteers was conducted at Queen Elizabeth Central Hospital in Blantyre, Malawi. Participants were randomly allocated to receive MV130 or placebo sublingually once daily for 42 days. Mucosal inflammation (neutrophil to T cell ratio, NTR) was measured in nasal micro-biopsies. Post-treatment, participants were challenged with 160,000 CFU/naris S. pneumoniae 6B (Spn6b). Experimental pneumococcal carriage rates post inoculation were compared between the two arms. All participants completing the study were included in the analysis. Prospective trial registration: PACTR202403820001276. FINDINGS: 107 participants were enrolled and randomised to MV130/placebo between May and December 2024. There were no serious adverse events, complete compliance was good (72%) and all adverse events were mild. 96 participants (53 male, 43 female) completed the study with 52 participants randomised to MV130 and 44 to placebo. There was no difference in mucosal inflammation (neutrophil to T cell ratio) at day 14 of the intervention MV130 NTR median = 0.737 (IQR 0.294, 2.059) and placebo NTR = 0.831 (IQR 0.450, 2.073), p = 0.64. Secondary analyses showed a rise in mucosal neutrophils after MV130 treatment and after experimental pneumococcal inoculation. There was no difference in nasal or serum anti-pneumococcal immunoglobulin or in experimental pneumococcal carriage proportion between MV130 (12/52, 23%) and placebo (10/44, 23%) groups (unadjusted risk ratio 1.02 (CI 0.49-2.12) p = 1.0). INTERPRETATION: MV130 induced non-specific mild neutrophil inflammation of the nasal mucosa but had no protective effect against experimental human pneumococcal carriage. FUNDING: Wellcome Trust.

Humans↗
PubMed2025

Innate immune molecular landscape following controlled human influenza virus infection.

Viral infections can induce prolonged changes in innate immunity. Here, we use blood samples from a human influenza H3N2 challenge study (NCT03883113) to perform comprehensive multi-omics analyses. We detect remodeling of immune programs in circulating innate immune cells that persist after resolution of the infection. We find changes associated with suppressed inflammation, including decreased cytokine and AP-1 gene expression as well as decreased accessibility at AP-1 targets and interleukin-related gene promoter regions. We also find decreased histone deacetylase gene expression, increased MAP kinase gene expression, and increased accessibility at interferon-related gene promoter regions. Genes involved in inflammation and methylation remodeling show modulation of gene-chromatin site regulatory circuit activity. These results reveal a coordinated rewiring of the molecular landscape in innate immune cells induced by mild influenza virus infection.

Humans↗
PubMed1976

Vaccination against typhoid fever with a live oral vaccine.

A Salmonella typhi gal E mutant, designated Ty 21a, has been developed on the basis of virulence and protection studies with similar Salmonella typhimurium mutants in mice. Gal E mutants are characterized by a block in the enzyme UDP-4-galactose-epimerase. They owe their outstanding immunizing capacity when used in live oral vaccine to the fact that when galactose is supplied exogenously, as occurs in vivo, wild-type cell wall structures are synthesized. On the other hand, avirulence of these mutants is based upon the fact that when galactose is taken up it is partly accumulated as galactose-1-phosphate and UDP-galactose, which induces lysis of the bacteria. Strain S. typhi Ty 21a does not revert to wild type in vivo and in vitro. Its safety for man has been demonstrated in studies involving 137 adults and 370 children. S. typhi Ty 21a also has been shown to protect against challenge with virulent S. typhi in human volunteers.

Administration, Oral↗
PubMed1978

Double-blind confirmation and treatment of milk sensitivity.

A nine-year-old boy had seasonal and perennial allergic nasal and eye symptoms, as well as the allergic-tension-fatigue syndrome. The presence of milk sensitivity was demonstrated by repeated non-blind and double-blind dietary challenge. He responded well to sublingual milk therapy. The efficacy of this technique was confirmed twice by double-blind challenges.

Animals↗
PubMed1976

Double-blind clinical assessment of ribavirin (virazole) in the prevention of induced infection with type B influenza virus.

The prophylactic effectiveness of oral administration of ribavirin (1-beta-D-ribofuranosyl-1,24-triazole-3-carboxamide, virazole) against artificially induced influenza B infection was evaluated in a double-blind clinical trial. Fifteen seronegative men received ribavirin capsules (600 mg/day in three divided doses), and 15 other men received placebo capsules two days before the inoculation of 6.4 X 10(4) 50% tissue culture infective doses of influenza virus B/Georgia/26/74 and for eight days after challenge. Ten men (69%) in each of the two groups developed mild to severe influenzal illness. Of these, five placebo-treated men developed severe febrile illness, while only one drug-treated man had illness of comparable severity. Illness of moderate severity was observed in three placebo-treated conrols and two drug recipients. There was no difference between the frequencies of isolation of virus or the anitbody responses in the two groups. Ribavirin suppressed signs and symptoms induced by influenza B challenge, but its effectiveness was marginal.

Adult↗
PubMed2014

Engineering adeno-associated viruses for clinical gene therapy.

Clinical gene therapy has been increasingly successful owing both to an enhanced molecular understanding of human disease and to progressively improving gene delivery technologies. Among these technologies, delivery vectors based on adeno-associated viruses (AAVs) have emerged as safe and effective and, in one recent case, have led to regulatory approval. Although shortcomings in viral vector properties will render extension of such successes to many other human diseases challenging, new approaches to engineer and improve AAV vectors and their genetic cargo are increasingly helping to overcome these barriers.

Capsid↗
PubMed1978

The functional relationship between artificial food colors and hyperactivity.

The presence of a functional relationship between the ingestion of artificial food colors and an increase in the frequency and/or duration of selected behaviors that are representative of the hyperactive behavior syndrome was experimentally investigated. Two eight-year-old females, who had been on the Feingold K-P diet for a minimum of 11 months, were the subjects studied. The experimental design was a variation of the BAB design, with double-blind conditions. This design allowed an experimental analysis of the placebo phases as well as challenge phases. Data were obtained by trained observers on Out of Seat, On Task, and Physically Aggressive behaviors, as they occurred in the subjects' regular class setting. Results indicated (a) the existence of a functional relationship between the ingestion of artificial food colors and an increase in both the duration and frequency of hyperactive behaviors, (b) the absence of a placebo effect, and (c) differential sensitivity of the dependent variables to the challenge effects.

Child↗
PubMed1978

Cooperative clinical trials and community outreach: the conceptual approach in Northern California.

Despite major advances in cancer treatment, one of the major challenges in oncology is the integration of community oncology and clinical research. A balance needs to be achieved between efforts to increase patient accrual into protocols and education designed to achieve minimal standards of care. The planning efforts in Northern California are one approach to the challenge, but it will take years before answers are available.

California↗
PubMed1976

The response of normal and asthmatic subjects to prostaglandins E2 and F2alpha by different routes, and their significance in asthma.

Although PGE2 and PGF2alpha have potent effects on the human bronchus by aerosol, they are less potent when given by the intravenous route. Prostaglandin E2 may cause bronchoconstriction. Indomethacin had no effect on day-to-day asthmatic symptoms, or challenge-induced asthma, suggesting that prostaglandins are not fundamental to the pathogenesis of asthma.

Adolescent↗
PubMed1976

Immunization of man and animals against influenza by oral and intranasal routes.

Live human and equine influenza virus strains modified by serial passage on allantois-on-shell system (AOS) in the presence of normal horse serum were administered orally or intranasally to volunteers or horses. Mostly mild clinical short-lasting reactions, replication in nasal mucosae, transmission to placebo recipients and significant local or circulating antibody rises were observed following administration to volunteers of strains modified by five or less serial passages on AOS in the presence of normal horse serum (NHS). Milder clinical reactions, no replication, no viral transmission and lower immunogenicity were observed when up to ten serial passages on AOS+ NHS were carried out. Similar results were observed in horses and colts. Heavy shedding of A/Eq-2 strain following the challenge was observed in placebo recipients. Colts immunized intranasally were completely protected while 33% of those immunized orally shedded small quantities of A/Eq-1 and A/Eq-2 viruses. However, a sharp rise of local antibodies against both strains was measured two days after the challenge in the three groups.

Administration, Intranasal↗
PubMed1978

Appraisal of skin tests with food extracts for diagnosis of food hypersensitivity.

Seventy-six children aged 5 months to 15 years who exhibited a net weal of 3.0 mm or greater to a puncture skin test with one or more of fourteen foods were subjected to double-blind food challenge. Confirmed reactions to double-blind food challenge were found to occur only with peanut, milk, egg and soybean. Puncture skin tests with 1:20 w/v concentration of food extracts identified all subjects who exhibited an adverse reaction during the double-blind food challenge. Performance of intradermal skin tests did not identify any additional subjects who reacted clinically to double-blind food challenge.

Adolescent↗