Intercell (Austria)

Abstract Background Colorectal cancer is the second leading cause of cancer-related fatalities. Recent genome-wide association studies (GWAS) identified genetic loci implicated in colorectal cancer susceptibility. This study aimed to uncover genetic factors influencing colorectal cancer rates among different populations, particularly in East Asia where prevalence is increasing. Methods A total of 423 colorectal cancer-associated single-nucleotide polymorphisms (SNPs) in the GWAS catalog were examined. Allele frequencies of these SNPs were analyzed across various populations. Data on allele frequencies at the population level were sourced from the 1000 Genomes Project and the Korean Reference Genome Database. We used Fisher's exact test to determine if the effect allele at a specific SNP was significantly overrepresented or underrepresented. Results Allele frequencies varied across populations. East Asians and Koreans showed similar patterns, distinct from Europeans. They also displayed higher genetic risk scores, correlating with colorectal cancer incidence. Conclusions Disparities in allele frequencies of colorectal cancer -associated SNPs were identified across populations, particularly between Koreans and other ethnic groups. These distinctions may help elucidate the heightened colorectal cancer prevalence, primarily among Koreans and East Asians. Our study underscores that genetic dissimilarities can, in part, account for the variance in colorectal cancer occurrence among diverse population subgroups.

A patch vaccine containing heat-labile toxin (LT) from enterotoxigenic Escherichia coli (ETEC) has demonstrated to be beneficial in reducing the rate and severity of travelers' diarrhea in Latin America. To evaluate the efficacy of this transdermal vaccine system in an area with a different diarrheal pathogen profile, an additional phase 2 study was conducted in European travelers to India. For this multicenter, randomized, double-blinded, placebo-controlled field study 723 subjects were recruited; 603 (299 LT vaccine, 304 placebo) were included in the per-protocol-population (PPP). Although the LT patch induced a measurable LT immune response in recipients, it failed to protect against LT ETEC or all-cause diarrhea. In the PPP the incidence rate of diarrhea as per primary endpoint was 6.0% (18 of 299) in the vaccine group and 5.9% (18 of 304) in the placebo group. Additionally, lower than expected rates of LT ETEC diarrheas were observed in India. The vaccine delivery system frequently produced rash and pruritus at the site of application, long term hyperpigmentation persisted in a minority of LT recipients, and also few site reactions were noted in the placebo group. The evaluated patch vaccine failed to satisfy mainly with respect to protective efficacy. Noninvasive prophylactic agents against travelers' diarrhea, particularly vaccines against the most frequent pathogens, thus continue to be badly needed.

The burden of Japanese encephalitis (JE) remains substantial despite increasing JE vaccine coverage [1]. Mouse-brain-derived (MB) JE vaccines are being replaced by second-generation JE vaccines pro...

Germinal centers are structures that promote humoral memory cell formation and affinity maturation, but the triggers for their development are not entirely clear. Activated extrafollicular B cells can form IgM-producing plasmablasts or enter a germinal center reaction and differentiate into memory or plasma cells, mostly of the IgG isotype. Vesicular stomatitis virus (VSV) induces both types of response, allowing events that promote each of these pathways to be studied. In this work, extrafollicular vs germinal center responses were examined at a cellular level, analyzing VSV-specific B cells in infected mice. We show that VSV-specific germinal centers are transiently formed when insufficient proportions of specific T cell help is available and that strong B cell activation in cells expressing high levels of the VSV-specific BCR promoted their differentiation into early blasts, whereas moderate stimulation of B cells or interaction with Th cells restricted extrafollicular responses and promoted germinal center formation.

The management of staphylococcal diseases is increasingly difficult with present medical approaches. Preventive and therapeutic vaccination is considered to be a promising alternative; however, little is known about immune correlates of protection and disease susceptibility. To better understand the immune recognition of Staphylococcus aureus by the human host, we studied the antistaphylococcal humoral responses in healthy people in comparison to those of patients with invasive diseases. In a series of enzyme-linked immunosorbent assay analyses performed using 19 recombinant staphylococcal cell surface and secreted proteins, we measured a wide range of antibody levels, finding a pronounced heterogeneity among individuals in both donor groups. The analysis revealed marked differences in the antibody repertoires of healthy individuals with or without S. aureus carriage, as well as in those of patients in the acute phase of infection. Most importantly, we identified antigenic proteins for which specific antibodies were missing or underrepresented in infected patients. In contrast to the well-described transient nature of disease-induced antistaphylococcal immune response, it was demonstrated that high-titer antistaphylococcal antibodies are stable for years in healthy individuals. In addition, we provide evidence obtained on the basis of opsonophagocytic and neutralizing activity in vitro assays that circulating antistaphylococcal serum antibodies in healthy donors are functional. In light of these data we suggest that proper serological analysis comparing the preexisting antibody repertoires of hospitalized patients with different outcomes for nosocomial staphylococcal infections could be extremely useful for the evaluation of candidate vaccine antigens in addition to protection data generated with animal models.