Biology subjects

Bushmaker, T.

Publications and source records attributed to Bushmaker, T..

3 recordsLinked to original sources

bioRxiv2020

ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.

microbiology↗

bioRxiv2020

A single dose of ChAdOx1 MERS provides broad protective immunity against a variety of MERS-CoV strains

Middle East respiratory syndrome coronavirus (MERS-CoV) continues to infect humans via the dromedary camel reservoir and can transmit between humans, most commonly via nosocomial transmission. Currently, no licensed vaccine is available. Previously we showed that vaccination of transgenic mice with ChAdOx1 MERS, encoding the MERS S protein, prevented disease upon lethal challenge. In the current study we show that rhesus macaques seroconverted rapidly after a single intramuscular vaccination with ChAdOx1 MERS. Upon MERS-CoV challenge vaccinated animals were protected against respiratory injury and pneumonia and had a reduction in viral load in lung tissue of several logs. Furthermore, we did not detect MERS-CoV replication in type I and II pneumocytes of ChAdOx1 MERS vaccinated animals. A prime-boost regimen of ChAdOx1 MERS boosted antibody titers, and viral replication was completely absent from the respiratory tract tissue of these rhesus macaques. Finally, we investigated the ability of ChAdOx1 MERS to protect against six different MERS-CoV strains, isolated between 2012 to 2018, from dromedary camels and humans in the Middle East and Africa. Antibodies elicited by ChAdOx1 MERS in rhesus macaques were able to neutralize all MERS-CoV strains. Vaccination of transgenic hDPP4 mice with ChAdOx1 MERS completely protected the animals against disease and lethality for all different MERS-CoV strains. The data support further clinical development of ChAdOx1 MERS supported by CEPI. One Sentence SummaryPrime-only vaccination with ChAdOx1 MERS provides protective immunity against HCoV-EMC/2012 replication in rhesus macaques, and a wide variety of MERS-CoV strains in mice.

microbiology↗

bioRxiv2019

Lek-associated movement of a putative Ebolavirus reservoir, the Hammer-headed fruit bat (Hypsignathus monstrosus), in northern Republic of Congo

The biology and ecology of Africas largest fruit bat remains largely understudied and enigmatic despite at least two highly unusual attributes. The acoustic lek mating behavior of the hammer-headed bat (Hypsignathus monstrosus) in the Congo basin was first described in the 1970s. Then in the 2000s, molecular testing implicated this species and other fruit bats as potential reservoir hosts for Ebola virus and it was one of only two fruit bat species epidemiologically linked to the 2008 Luebo, Democratic Republic of Congo, Ebola outbreak. Here we share findings from the first pilot study of hammer-headed bat movement using GPS tracking and accelerometry units and a small preceding radio-tracking trial at an apparent lekking site. The radio-tracking revealed adult males had high rates of nightly visitation to the site compared to females (only one visit) and that two of six females day-roosted [~]100 m west of Libonga, the nearest village that is [~]1.6 km southwest. Four months later, in mid-April 2018, five individual bats, comprised of four males and one female, were tracked from two to 306 days, collecting from 67 to 1022 GPS locations. As measured by mean distance to the site and proportion of nightly GPS locations within 1 km of the site (percent visitation), the males were much more closely associated with the site (mean distance 1.4 km; 51% visitation), than the female (mean 5.5 km; 2.2% visitation). Despite the small sample size, our tracking evidence supports our original characterization of the site as a lek, and the lek itself is much more central to male than female movement. Moreover, our pilot demonstrates the technical feasibility of executing future studies on hammer-headed bats that will help fill problematic knowledge gaps about zoonotic spillover risks and the conservation needs of fruit bats across the continent.

ecology↗