Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) among travellers to Africa: destination-specific data pooled from three European prospective studies.

BACKGROUND: One third of travellers to low- and middle-income regions of the tropics and subtropics become colonized by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). The risk varies by destination and, for each traveller, may be substantially further increased by travellers' diarrhoea (TD) and antibiotic use. Despite the risk of TD in Africa, ESBL-PE acquisition rates in all studies are lower there than in Asia. Africa has become increasingly popular as a destination for international travellers, yet minimal data are available from the continent's subregions and countries. METHODS: We analysed subregion- and country-specific data on carriage and risk factors for ESBL-PE colonization pooled from three prospective studies conducted between 2009 and 2013 among Finnish and Dutch travellers. The data were subjected to multivariable analysis of risk factors. In addition, we compared our data to two recent large investigations reporting data by subregion and country. RESULTS: Our joint analysis comprised data on 396 travellers. The ESBL-PE colonization rate was highest in Northern Africa, followed by Middle and Eastern Africa, and lowest in Southern and Western Africa. Of individual countries with more than 15 visitors, the highest rates were seen for Egypt (12/17; 70.6%), Ghana (6/23; 26.1%), and Tanzania (14/81; 17.3%); the rates among travellers to Egypt were comparable to those reported in South and Southeast Asia. In a pooled multivariable analysis, travel destination, age, overnight hospitalisation abroad, TD, and use of fluoroquinolones were independently associated with increased ESBL-PE colonization rates. CONLUSIONS: Even in areas with relatively low risk of colonization, antimicrobials clearly predispose to colonization with ESBL-PE. Travellers to Africa should be cautioned against unnecessary use of antibiotics.

Vaccine-Induced Antibody Responses against SARS-CoV-2 Variants-Of-Concern Six Months after the BNT162b2 COVID-19 mRNA Vaccination.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has raised concern about increased transmissibility, infectivity, and immune evasion from a vaccine and infection-induced immune responses. Although COVID-19 mRNA vaccines have proven to be highly effective against severe COVID-19 disease, the decrease in vaccine efficacy against emerged Beta and Delta variants emphasizes the need for constant monitoring of new virus lineages and studies on the persistence of vaccine-induced neutralizing antibodies. To analyze the dynamics of COVID-19 mRNA vaccine-induced antibody responses, we followed 52 health care workers in Finland for 6 months after receiving two doses of BNT162b2 vaccine with a 3-week interval. We demonstrate that, although anti-S1 antibody levels decrease 2.3-fold compared to peak antibody levels, anti-SARS-CoV-2 antibodies persist for months after BNT162b2 vaccination. Variants D614G, Alpha, and Eta are neutralized by sera of 100% of vaccinees, whereas neutralization of Delta is 3.8-fold reduced and neutralization of Beta is 5.8-fold reduced compared to D614G. Despite this reduction, 85% of sera collected 6 months postvaccination neutralizes Delta variant. IMPORTANCE A decrease in vaccine efficacy against emerging SARS-CoV-2 variants has increased the importance of assessing the persistence of SARS-CoV-2 spike protein-specific antibodies and neutralizing antibodies. Our data show that after 6 months post two doses of BNT162b2 vaccine, antibody levels decrease yet remain detectable and capable of neutralizing emerging variants. By monitoring the vaccine-induced antibody responses, vaccination strategies and administration of booster doses can be optimized.

Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants.

Two COVID-19 mRNA (of BNT162b2, mRNA-1273) and two adenovirus vector vaccines (ChAdOx1 and Janssen) are licensed in Europe, but optimization of regime and dosing is still ongoing. Here we show in health care workers (n = 328) that two doses of BNT162b2, mRNA-1273, or a combination of ChAdOx1 adenovirus vector and mRNA vaccines administrated with a long 12-week dose interval induce equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against D614 and Delta variant. By contrast, two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies than those from the 12-week interval, yet a third BNT162b2 or mRNA-1273 booster dose increases the antibody levels 4-fold compared to the levels after the second dose, as well as induces neutralizing antibody against Omicron BA.1 variant. Our data thus indicates that a third COVID-19 mRNA vaccine may induce cross-protective neutralizing antibodies against multiple variants.

COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants.

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees' neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants.