Streptobacillus moniliformis With Features of Hemophagocytic Lymphohistiocytosis Identified by Direct Sequencing.

Rat-bite fever caused by Streptobacillus moniliformis is a rare infection that may be fatal. An adolescent male presented with multiorgan failure, negative blood cultures and Gram-negative rods in blood smear. S. moniliformis was identified by 16S ribosomal RNA gene sequencing from the blood. He developed systemic hyperinflammatory syndrome resembling hemophagocytic lymphohistiocytosis, for which immune-globulins and steroids were added to the antibiotic regimen and he rapidly recovered.

DNA and modified vaccinia virus Ankara vaccines encoding multiple cytotoxic and helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) are safe but weakly immunogenic in HIV-1-uninfected, vaccinia virus-naive adults.

We evaluated a DNA plasmid-vectored vaccine and a recombinant modified vaccinia virus Ankara vaccine (MVA-mBN32), each encoding cytotoxic and helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) in a randomized, double-blinded, placebo-controlled trial in 36 HIV-1-uninfected adults using a heterologous prime-boost schedule. HIV-1-specific cellular immune responses, measured as interleukin-2 and/or gamma interferon production, were induced in 1 (4%) of 28 subjects after the first MVA-mBN32 immunization and in 3 (12%) of 25 subjects after the second MVA-mBN32 immunization. Among these responders, polyfunctional T-cell responses, including the production of tumor necrosis factor alpha and perforin, were detected. Vaccinia virus-specific antibodies were induced to the MVA vector in 27 (93%) of 29 and 26 (93%) of 28 subjects after the first and second immunizations with MVA-mBN32. These peptide-based vaccines were safe but were ineffective at inducing HIV-1-specific immune responses and induced much weaker responses than MVA vaccines expressing the entire open reading frames of HIV-1 proteins.

Serological immunity to adenovirus serotype 5 is not associated with risk of HIV infection: a case-control study.

BACKGROUND: adenoviruses are among the most promising vectors for the development of an HIV vaccine. The results of the phase IIB study of the adenovirus serotype 5-based Merck Trivalent HIV vaccine have raised the concern that serological immunity to adenovirus serotype 5 (Ad5) could be linked to HIV acquisition risk in high-risk individuals. We examined the association between adenovirus serostatus and the rate of incident HIV infection in populations at elevated risk of HIV acquisition. METHODS: we performed a nested case-control study of Ad5 serostatus among 299 HIV-infected and 590 matched HIV-uninfected persons participating in the Multicenter AIDS Cohort Study (MACS) and in HPTN 039, a study of herpes simplex virus 2 suppression among adults in the United States, South America, and Africa. Appropriate HIV cases and controls were identified in each cohort, and Ad5-neutralizing antibody titers were compared in these two groups. RESULTS: in MACS and HPTN 039, the relative risks of incident HIV infection among Ad5-seropositive vs. Ad5-seronegative individuals were 1.1 (95% confidence interval 0.8-1.5, P = 0.57) and 1.0 (95% confidence interval 0.4-2.3, P = 0.99), respectively. HIV-1 acquisition rates did not vary significantly by Ad5-neutralizing antibody titer. CONCLUSION: the presence of Ad5-neutralizing antibodies is not linked to the risk of HIV acquisition among populations at elevated risk of HIV infection.

Direct comparison of antigen production and induction of apoptosis by canarypox virus- and modified vaccinia virus ankara-human immunodeficiency virus vaccine vectors.

Recombinant poxvirus vectors are undergoing intensive evaluation as vaccine candidates for a variety of infectious pathogens. Avipoxviruses, such as canarypox virus, are replication deficient in mammalian cells by virtue of a poorly understood species-specific restriction. Highly attenuated vaccinia virus strains such as modified vaccinia virus Ankara (MVA) are similarly unable to complete replication in most mammalian cells but have an abortive-late phenotype, in that the block to replication occurs post-virus-specific DNA replication. In this study, an identical expression cassette for human immunodeficiency virus gag, pro, and env coding sequences was placed in canarypox virus and MVA vector backbones in order to directly compare vector-borne expression and to analyze differences in vector-host cell interactions. Antigen production by recombinant MVA was shown to be greater than that from recombinant canarypox virus in the mammalian cell lines and in the primary human cells tested. This observation was primarily due to a longer duration of antigen production in recombinant MVA-infected cells. Apoptosis induction was found to be more profound with the empty canarypox virus vector than with MVA. Remarkably, however, the inclusion of a gag/pro/env expression cassette altered the kinetics of apoptosis induction in recombinant MVA-infected cells to levels equal to those found in canarypox virus-infected cells. Antigen production by MVA was noted to be greater in human dendritic cells and resulted in enhanced T-cell stimulation in an in vitro antigen presentation assay. These results reveal differences in poxvirus vector-host cell interactions that should be relevant to their use as immunization vehicles.