Yeast-produced subunit protein vaccine elicits broadly neutralizing antibodies that protect mice against Zika virus lethal infection

International audienceZika virus (ZIKV) infection is a serious public health concern due to its ability to induce neurological defects and its potential for rapid transmission at a global scale. However, no vaccine is currently available to prevent ZIKV infection. Here, we report the development of a yeast-derived subunit protein vaccine for ZIKV. The envelope protein domain III (EDIII) of ZIKV was produced as a secretory protein in the yeast Pichia pastoris. The yeast-derived EDIII could inhibit ZIKV infection in vitro in a dose-dependent manner, suggesting that it had acquired an appropriate conformation to bind to cellular receptors of ZIKV. Immunization with recombinant EDIII protein effectively induced antigen-specific binding antibodies and cellular immune responses. The resulting anti-EDIII sera could efficiently neutralize ZIKV representative strains from both Asian and African lineages. Passive transfer with the anti-EDIII neutralizing sera could confer protection against lethal ZIKV challenge in mice. Importantly, we found that purified anti-EDIII antibodies did not cross-react with closely related dengue virus (DENV) and therefore did not enhance DENV infection. Collectively, our results demonstrate that yeast-produced EDIII is a safe and effective ZIKV vaccine candidate

Zika vector competence data reveals risks of outbreaks: the contribution of the European ZIKAlliance project

First identified in 1947, Zika virus took roughly 70 years to cause a pandemic unusually associated with virus-induced brain damage in newborns. Zika virus is transmitted by mosquitoes, mainly Aedes aegypti, and secondarily, Aedes albopictus, both colonizing a large strip encompassing tropical and temperate regions. As part of the international project ZIKAlliance initiated in 2016, 50 mosquito populations from six species collected in 12 countries were experimentally infected with different Zika viruses. Here, we show that Ae. aegypti is mainly responsible for Zika virus transmission having the highest susceptibility to viral infections. Other species play a secondary role in transmission while Culex mosquitoes are largely non-susceptible. Zika strain is expected to significantly modulate transmission efficiency with African strains being more likely to cause an outbreak. As the distribution of Ae. aegypti will doubtless expand with climate change and without new marketed vaccines, all the ingredients are in place to relive a new pandemic of Zika

Zika vector competence data reveals risks of outbreaks: the contribution of the European ZIKAlliance project

First identified in 1947, Zika virus took roughly 70 years to cause a pandemic unusually associated with virus-induced brain damage in newborns. Zika virus is transmitted by mosquitoes, mainly Aedes aegypti, and secondarily, Aedes albopictus, both colonizing a large strip encompassing tropical and temperate regions. As part of the international project ZIKAlliance initiated in 2016, 50 mosquito populations from six species collected in 12 countries were experimentally infected with different Zika viruses. Here, we show that Ae. aegypti is mainly responsible for Zika virus transmission having the highest susceptibility to viral infections. Other species play a secondary role in transmission while Culex mosquitoes are largely non-susceptible. Zika strain is expected to significantly modulate transmission efficiency with African strains being more likely to cause an outbreak. As the distribution of Ae. aegypti will doubtless expand with climate change and without new marketed vaccines, all the ingredients are in place to relive a new pandemic of Zika.info:eu-repo/semantics/publishedVersio

The Impact of Different Antibiotic Regimens on the Emergence of Antimicrobial-Resistant Bacteria

Backgroud: The emergence and ongoing spread of antimicrobial-resistant bacteria is a major public health threat. Infections caused by antimicrobial-resistant bacteria are associated with substantially higher rates of morbidity and mortality compared to infections caused by antimicrobial-susceptible bacteria. The emergence and spread of these bacteria is complex and requires incorporating numerous interrelated factors which clinical studies cannot adequately address. Methods/Principal Findings: A model is created which incorporates several key factors contributing to the emergence and spread of resistant bacteria including the effects of the immune system, acquisition of resistance genes and antimicrobial exposure. The model identifies key strategies which would limit the emergence of antimicrobial-resistant bacterial strains. Specifically, the simulations show that early initiation of antimicrobial therapy and combination therapy with two antibiotics prevents the emergence of resistant bacteria, whereas shorter courses of therapy and sequential administration of antibiotics promote the emergence of resistant strains. Conclusions/Significance: The principal findings suggest that (i) shorter lengths of antibiotic therapy and early interruption of antibiotic therapy provide an advantage for the resistant strains, (ii) combination therapy with two antibiotics prevents the emergence of resistance strains in contrast to sequential antibiotic therapy, and (iii) early initiation of antibiotics is among the most important factors preventing the emergence of resistant strains. These findings provide new insights into strategies aimed at optimizing the administration of antimicrobials for the treatment of infections and the prevention of the emergence of antimicrobial resistance

Zika vector competence data reveals risks of outbreaks: the contribution of the European ZIKAlliance project

First identified in 1947, Zika virus took roughly 70 years to cause a pandemic unusually associated with virus-induced brain damage in newborns. Zika virus is transmitted by mosquitoes, mainly Aedes aegypti, and secondarily, Aedes albopictus, both colonizing a large strip encompassing tropical and temperate regions. As part of the international project ZIKAlliance initiated in 2016, 50 mosquito populations from six species collected in 12 countries were experimentally infected with different Zika viruses. Here, we show that Ae. aegypti is mainly responsible for Zika virus transmission having the highest susceptibility to viral infections. Other species play a secondary role in transmission while Culex mosquitoes are largely non-susceptible. Zika strain is expected to significantly modulate transmission efficiency with African strains being more likely to cause an outbreak. As the distribution of Ae. aegypti will doubtless expand with climate change and without new marketed vaccines, all the ingredients are in place to relive a new pandemic of Zika

Vector competence of Aedes aegypti from New Caledonia for the four recent circulating dengue virus serotypes

International audienceIn New Caledonia (NC), Aedes aegypti is the only proven vector of dengue virus (DENV), which is the most prevalent arbovirosis in NC. Since World War II, the four DENV serotypes have circulated regularly in NC. The epidemiological profile, however, has evolved over the last ten years, with the persistence of DENV-1 circulation and the co-circulation of several DENV serotypes. The current study evaluated the ability of Ae. aegypti from NC to transmit four DENV serotypes (and two DENV-1 genotypes) isolated during recent outbreaks in NC. An Ae. aegypti F1 generation was twice independently orally challenged with each DENV strain (107 FFU/ml). Infection, dissemination and transmission rates and transmission efficiency were measured at day 7 and 14 post-exposure, as well as the quantity of infectious virus particles. Mosquito infection was observed as early as 7 days post-infection. Infection rates between 18 and 58% were measured for all DENV serotypes/genotypes tested. Although dissemination rates ranged from 78 to 100%, transmission efficiencies were low, with values not exceeding 21% at 14 days post-infection for all DENV strains. This study shows that NC Ae. aegypti are moderately competent for DENV in laboratory conditions. In link with epidemiological data, these results suggest implication of other factors in the sustained circulation of DENV-1 in New Caledonia

Successful COVID-19 elimination after an alpha variant outbreak in a “safe travel zone”

International audienc