The use of classical smallpox vaccines based on vaccinia virus (VV) is associated with severe complications in both naïve and immune individuals. Modified vaccinia virus Ankara (MVA), a highly attenuated replicationdeficient strain of VV, has been proven to be safe in humans and immunocompromised animals, and its efficacy against smallpox is currently being addressed. Here we directly compare the efficacies of MVA alone and in combination with classical VV-based vaccines in a cynomolgus macaque monkeypox model. The MVA-based smallpox vaccine protected macaques against a lethal respiratory challenge with monkeypox virus and is therefore an important candidate for the protection of humans against smallpox.

BackgroundUnprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI) of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be produced rapidly and in sufficient quantities. Potential pandemic inactivated vaccines will ideally induce substantial intra-subtypic cross-protection in humans to warrant the option of use, either prior to or just after the start of a pandemic outbreak. In the present study, we evaluated a split H5N1 A/H5N1/Vietnam/1194/04, clade 1 candidate vaccine, adjuvanted with a proprietary oil-in- water emulsion based Adjuvant System proven to be well-tolerated and highly immunogenic in the human (Leroux-Roels et al. (2007) The Lancet 370:580–589), for its ability to induce intra-subtypic cross-protection against clade 2 H5N1/A/Indonesia/5/05 challenge in ferrets.Methodology and Principal FindingsAll ferrets in control groups receiving non-adjuvanted vaccine or adjuvant alone failed to develop specific or cross-reactive neutralizing antibodies and all died or had to be euthanized within four days of virus challenge. Two doses of adjuvanted split H5N1 vaccine containing ≥1.7 µg HA induced neutralizing antibodies in the majority of ferrets to both clade 1 (17/23 (74%) responders) and clade 2 viruses (14/23 (61%) responders), and 96% (22/23) of vaccinees survived the lethal challenge. Furthermore lung virus loads and viral shedding in the upper respiratory tract were reduced in vaccinated animals relative to controls suggesting that vaccination might also confer a reduced risk of viral transmission.ConclusionThese protection data in a stringent challenge model in association with an excellent clinical profile highlight the potential of this adjuvanted H5N1 candidate vaccine as an effective tool in pandemic preparedness.

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Twenty Ni-reactive T-lymphocyte clones were obtained from eight different donors and analyzed for their ability to cross-react with other metals. All Ni-reactive T-lymphocyte clones were CD4+CD8- and recognized Ni in association with either HLA-DR or -DQ molecules. Based on the periodic table of the elements, the metals Cr, Fe, Co, Cu, and Zn from the same horizontal row as Ni, and Pd and Pt from the same vertical row, were selected to study T-lymphocyte clone cross-reactivity. Distinct cross-reactivity patterns were found that could be divided into three major groups: Ni-reactive T-lymphocyte clones i) cross-reacting with Cu, ii) cross-reacting with Pd, or iii) without cross-reactivity. Major histocompatibility complex class II-restriction patterns of Cu- and Pd-induced proliferative responses did not differ from those for the Ni-induced responses. In vitro cross-reactivities with Cu and Pd may be favored by their bivalency and location next to Ni in the periodic table, and the similarity of these metals to Ni in binding to histidine residues of peptides in the pocket of major histocompatibility complex class II molecules. The present findings suggest that Cu and Pd hypersensitivities, which are occasionally observed in Ni-allergic patients, may be due to cross-reactivities at the T-cell clonal level rather than to concomitant sensitization.