Selective replication and vertical transmission of Ebola virus in experimentally infected Angolan free-tailed bats.

The natural reservoir of Ebola virus (EBOV), agent of a zoonosis burdening several African countries, remains unidentified, albeit evidence points towards bats. In contrast, the ecology of the related Marburg virus is much better understood; with experimental infections of bats being instrumental for understanding reservoir-pathogen interactions. Experiments have focused on elucidating reservoir competence, infection kinetics and specifically horizontal transmission, although, vertical transmission plays a key role in many viral enzootic cycles.

Tolerance and Persistence of Ebola Virus in Primary Cells from , a Potential Ebola Virus Reservoir.

Although there have been documented Ebola virus disease outbreaks for more than 40 years, the natural reservoir host has not been identified. Recent studies provide evidence that the Angolan free-tailed bat (), an insectivorous microbat, is a possible ebolavirus reservoir. To investigate the potential role of this bat species in the ecology of ebolaviruses, replication, tolerance, and persistence of Ebola virus (EBOV) were investigated in 10 different primary bat cell isolates from .

Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir - .

Lassa virus (LASV), a Risk Group-4 zoonotic haemorrhagic fever virus, affects sub-Saharan African countries. Lassa fever, caused by LASV, results in thousands of annual deaths. Although decades have elapsed since the identification of the Natal multimammate mouse () as a natural reservoir of LASV, little effort has been made to characterize LASV infection in its reservoir.

Development of an Efficacious, Semisynthetic Glycoconjugate Vaccine Candidate against Serotype 1.

Infections with are a major health burden. Glycoconjugate vaccines based on capsular polysaccharides (CPSs) successfully protect from infection, but not all pneumococcal serotypes are covered with equal potency. Marketed glycoconjugate vaccines induce low levels of functional antibodies against the highly invasive serotype 1 (ST1), presumably due to the obscuring of protective epitopes during chemical activation and conjugation to carrier proteins.

A semisynthetic serotype 8 glycoconjugate vaccine.

Glycoconjugate vaccines based on capsular polysaccharides (CPSs) of pathogenic bacteria such as successfully protect from disease but suffer from incomplete coverage, are troublesome to manufacture from isolated CPSs, and lack efficacy against certain serotypes. Defined, synthetic oligosaccharides are an attractive alternative to isolated CPSs but require the identification of immunogenic and protective oligosaccharide antigens. We describe a medicinal chemistry strategy based on a combination of automated glycan assembly (AGA), glycan microarray-based monoclonal antibody (mAb) reverse engineering, and immunological evaluation in vivo to uncover a protective glycan epitope (glycotope) for serotype 8 (ST8).

A Semi-synthetic Oligosaccharide Conjugate Vaccine Candidate Confers Protection against Streptococcus pneumoniae Serotype 3 Infection.

The identification of immunogenic glycotopes that render glycoconjugate vaccines protective is key to improving vaccine efficacy. Synthetic oligosaccharides are an attractive alternative to the heterogeneous preparations of purified polysaccharides that most marketed glycoconjugate vaccines are based on. To investigate the potency of semi-synthetic glycoconjugates, we chose the least-efficient serotype in the current pneumococcal conjugate vaccine Prevnar 13, Streptococcus pneumoniae serotype 3 (ST3).

Multivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans.

Synthetic cell-surface glycans are promising vaccine candidates against Clostridium difficile. The complexity of large, highly antigenic and immunogenic glycans is a synthetic challenge. Less complex antigens providing similar immune responses are desirable for vaccine development.

Epitope recognition of antibodies against a Yersinia pestis lipopolysaccharide trisaccharide component.

Today, the process of selecting carbohydrate antigens as a basis for active vaccination and the generation of antibodies for therapeutic and diagnostic purposes is based on intuition combined with trial and error experiments. In efforts to establish a rational process for glycan epitope selection, we employed glycan array screening, surface plasmon resonance, and saturation transfer difference (STD)-NMR to elucidate the interactions between antibodies and glycans representing the Yersinia pestis lipopolysaccharide (LPS). A trisaccharide epitope of the LPS inner core glycan and different LPS-derived oligosaccharides from various Gram-negative bacteria were analyzed using this combination of techniques.

Immunogenicity and diagnostic potential of synthetic antigenic cell surface glycans of Leishmania.

Detection and quantification of pathogen-derived antigenic structures is a key method for the initial diagnosis and follow-up of various infectious diseases. Complex parasitic diseases such as leishmaniasis require highly sensitive and specific tests prior to treatment with potentially toxic drugs. To investigate the diagnostic potential of cell surface glycans found on Leishmania parasites, we identified diagnostically relevant glycan epitopes and used synthetic glycan microarrays to screen sera from infected humans and dogs.