Accelerated Development of COVID-19 Vaccines: Technology Platforms, Benefits, and Associated Risks.

Multiple preventive COVID-19 vaccines have been developed during the ongoing SARS coronavirus (CoV) 2 pandemic, utilizing a variety of technology platforms, which have different properties, advantages, and disadvantages. The acceleration in vaccine development required to combat the current pandemic is not at the expense of the necessary regulatory requirements, including robust and comprehensive data collection along with clinical product safety and efficacy evaluation. Due to the previous development of vaccine candidates against the related highly pathogenic coronaviruses SARS-CoV and MERS-CoV, the antigen that elicits immune protection is known: the surface spike protein of SARS-CoV-2 or specific domains encoded in that protein, e.g., the receptor binding domain. From a scientific point of view and in accordance with legal frameworks and regulatory practices, for the approval of a clinic trial, the Paul-Ehrlich-Institut requires preclinical testing of vaccine candidates, including general pharmacology and toxicology as well as immunogenicity. For COVID-19 vaccine candidates, based on existing platform technologies with a sufficiently broad data base, pharmacological-toxicological testing in the case of repeated administration, quantifying systemic distribution, and proof of vaccination protection in animal models can be carried out in parallel to phase 1 or 1/2 clinical trials. To reduce the theoretical risk of an increased respiratory illness through infection-enhancing antibodies or as a result of Th2 polarization and altered cytokine profiles of the immune response following vaccination, which are of specific concern for COVID-19 vaccines, appropriate investigative testing is imperative. In general, phase 1 (vaccine safety) and 2 (dose finding, vaccination schedule) clinical trials can be combined, and combined phase 2/3 trials are recommended to determine safety and efficacy. By applying these fundamental requirements not only for the approval and analysis of clinical trials but also for the regulatory evaluation during the assessment of marketing authorization applications, several efficacious and safe COVID-19 vaccines have been licensed in the EU by unprecedentedly fast and flexible procedures. Procedural and regulatory-scientific aspects of the COVID-19 licensing processes are described in this review.

Lead exposure by drinking water: an epidemiologial study in Hamburg, Germany.

Study objective was to investigate the extent of lead exposure via tap water in Hamburg and the relevance of preventive strategies. Two hundred and forty-eight non-smoking young women participated in the cross-sectional study program and 52 women completed the intervention program. In the cross-sectional study program most women (N = 178) didn't know anything about the material of the plumbing system at their homes. Participants with lead in the tap water above the detection limit of 5 microg/l (N = 142) showed significantly higher blood lead levels (median 31 microg/l) compared to those with no detectable lead in the tap water (N = 106; median blood lead 24 microg/l, p < = 0.001). There is a close correlation between the average lead concentration in the tap water and blood lead concentrations (N = 142 value pairs, Spearman's rho 0.43, p < = 0.0001). In the intervention program, the women were asked to minimize exposure by flushing water or to exclude it by consuming bottled water. Intervention lowered blood lead-level significantly (median decrease of 11 microg/l, p < = 0.001). "Minimizers" could lower their blood lead levels by about 21% of the initial value, "excluders" by about 37% (ns, p < = 0.17). The majority judged neither minimizing nor excluding tap water as practicable health preventive behaviour pattern in the long run. Lead in tap water stands for an avoidable surplus exposure. These results underline the relevance of health care preventive measures for the most sensitive groups.

Occurrence of toxigenic Aspergillus versicolor isolates and sterigmatocystin in carpet dust from damp indoor environments.

Over the past decade, there has been growing concern regarding the role of toxigenic fungi in damp indoor environments; however, there is still a lack of field investigations on exposure to mycotoxins. The goal of our pilot study was to quantify the proportion of toxigenic Aspergillus versicolor isolates in native carpet dust from damp dwellings with mold problems and to determine whether sterigmatocystin can be detected in this matrix. Carpet dust samples (n = 11) contained from <2.5 x 10(1) to 3.6 x 10(5) (median, 3.1 x 10(4)) A. versicolor CFU/g of dust, and the median proportion of A. versicolor from total culturable fungi was 18%. Based on thin-layer chromatography detection of sterigmatocystin, 49 of 50 A. versicolor isolates (98%) were found to be toxigenic in vitro. By using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry, sterigmatocystin could be detected in low concentrations (2 to 4 ng/g of dust) in 2 of 11 native carpet dust samples. From this preliminary study, we conclude that most strains of A. versicolor isolated from carpet dust are able to produce sterigmatocystin in vitro and that sterigmatocystin may occasionally occur in carpet dust from damp indoor environments. Further research and systematic field investigation are needed to confirm our results and to provide an understanding of the health implications of mycotoxins in indoor environments.