Booster response to 30 μg adjuvanted clade 2/ Indonesia/5/05-RG2 vaccine at 22 months following the first vaccination.

<p>Booster response to 30 μg adjuvanted clade 2/ Indonesia/5/05-RG2 vaccine at 22 months following the first vaccination.</p

Solicited adverse events following booster vaccination or in case of clade 2 primary vaccination within 3 to 7-days after vaccination.

<p>Solicited adverse events following booster vaccination or in case of clade 2 primary vaccination within 3 to 7-days after vaccination.</p

Antibody persistence as defined by HI antibody titer at 6/15/22-months following the first vaccination with clade 1 A/Vietnam/1194/2004/NIBERG-14.

<p>Antibody persistence as defined by HI antibody titer at 6/15/22-months following the first vaccination with clade 1 A/Vietnam/1194/2004/NIBERG-14.</p

21 Day Booster response to 7.5 μg clade 1 A/Vietnam/1194/2004/NIBERG-14 6-months after the first vaccination.

<p>21 Day Booster response to 7.5 μg clade 1 A/Vietnam/1194/2004/NIBERG-14 6-months after the first vaccination.</p

Primary response following clade 2 A/Indonesia /5/05-RG2 as determined by HIH method.

<p>Primary response following clade 2 A/Indonesia /5/05-RG2 as determined by HIH method.</p

DataSheet_1_A randomized, double-blind, placebo-controlled, dose-escalating phase I trial to evaluate safety and immunogenicity of a plant-produced, bivalent, recombinant norovirus-like particle vaccine.docx

Noroviruses (NoV) are the leading cause of epidemic acute gastroenteritis in humans worldwide and a safe and effective vaccine is needed. Here, a phase I, double-blind, placebo-controlled clinical trial was performed in 60 healthy adults, 18 to 40 years old. Safety (primary objective) and immunogenicity (secondary and exploratory objectives) of a bivalent (GI.4 and GII.4), plant-produced, virus-like particle (VLP), NoV vaccine candidate formulation were investigated at two dose levels (50 µg + 50 µg and 150 µg + 150 µg) without adjuvant. Overall, 13 subjects (65.0%) in the 50 µg group, 16 subjects (80.0%) in the 150 µg group, and 14 subjects (70.0%) in the placebo group reported at least 1 solicited local or general symptom during the 7-day post-vaccination periods following each dose. Severe solicited adverse events (AEs) were rare (2 events in the 50 µg group). A total of 8 subjects (40.0%) in each group reported at least one unsolicited AE during the 28-day post-vaccination periods. Immunogenicity was assessed on days 1, 8, 29, 57, 183 and 365. All subjects were pre-exposed to norovirus as indicated by baseline levels of the different immunological parameters examined. Vaccine-specific humoral and cellular immune responses increased after the first dose but did not rise further after the second vaccination. Increased GI.4- and GII.4-specific IgG titers persisted until day 365. The vaccine elicited cross-reactive IgG antibodies against non-vaccine NoV VLPs, which was more pronounced for NoV strains of the same genotype as the GII.4 vaccine strain than for non-vaccine genotypes. Significant blocking anti-GI.4 and anti-GII.4 VLP titers were triggered in both dose groups. Lymphoproliferation assays revealed strong cell-mediated immune responses that persisted until day 365. In conclusion, both dose levels were safe and well-tolerated, and no higher incidence of AEs was observed in the higher dose group. The data show that a single dose of the vaccine formulated at 50 µg of each VLP is sufficient to reach a peak immune response after 8 to 28 days. The results of this Phase I study warrant further evaluation of the non-adjuvanted vaccine candidate.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/record/NCT05508178, identifier (NCT05508178).</p

Phenotypic antibiotic resistance of colistin-resistant Enterobacterales.

(A) Stacked barplots of the proportion of isolates phenotypically resistant to a number of antibiotic classes. (B) Stacked barplots of the proportion of isolates phenotypically resistant to critically important antibiotics. AG: Aminoglycosides, COL: Colistin, ESC: Extended-spectrum cephalosporins, FQ: Fluoroquinolones, LTCF: Long-term care facility, BE: Belgium, NL: The Netherlands.</p

Fig 4 -

Genotypic fluoroquinolone resistance mutations (A) and resistance genes (B) for critically important antibiotics detected in colistin-resistant Enterobacterales. (A) Stacked barplots of the proportion of colistin-resistant E. coli and Klebsiella spp. with mutations in the quinolone-resistance determining regions (QRDR) linked to fluoroquinolone resistance. (B) Resistance genes for critically important antibiotics detected in colistin-resistant Enterobacterales. Each circle represents a genome (isolate) colored by species. Barplots show the number of genomes from the different sectors (top) and containing the resistance gene (right) colored by species. N: Naturally occurring genes, Kpn: K. pneumoniae, QRDR: Quinolone-resistance determining region, FQ: Fluoroquinolone, ESBL: Extended-spectrum beta-lactamase, * aminoglycoside genes linked to resistance to gentamicin, tobramycin.</p

Single alteration leading to colistin resistance (no other mutations in PmrAB and PhoPQ detected).

Single alteration leading to colistin resistance (no other mutations in PmrAB and PhoPQ detected).</p

Association of colistin resistance with prior colistin use in pig farms in Belgium (n = 14) and the Netherlands (n = 15).

Association of colistin resistance with prior colistin use in pig farms in Belgium (n = 14) and the Netherlands (n = 15).</p