Publications

Bovine and human respiratory syncytial virus (BRSV and HRSV) are major causes of respiratory disease in calves and children, respectively, and are prioritized vaccine targets. We previously demonstrated that an experimental vaccine, BRSV-immunostimulating complexes (ISCOMs), is effective in calves with maternal antibodies. The present study focused on antigenic characterization of this vaccine for the design of new generation subunit vaccines. Results confirmed the presence of G, F and N proteins in the ISCOMs and this knowledge was extended by the identification of M, M2-1, P and SH, as well as cellular membrane proteins such as integrin alphaVbeta1, alphaVbeta3 and alpha3beta1. The quantity of the major protein F was four- to five-fold greater than that of N ( approximately 77 mug vs. approximately 17 mug/calf dose), whereas G, M, M2-1, P and SH were likely present in smaller amounts. The L, M2-2, NS1 and NS2 proteins were not detected, suggesting that they are not essential for protection. Sera from BRSV-ISCOM immunized calves contained high titers of IgG antibody specific for F, G, N and SH. Antibody responses against M and P were not detected; however, this does not exclude their role in protective T cell responses. The absence of immunopathological effects of cellular proteins such as integrins needs to be further confirmed and their possible contribution to adjuvant functions requires elucidation. This work suggests that a combination of several surface and internal proteins should be included in subunit RSV vaccines and identifies absent proteins as potential candidates for differentiation of infected from vaccinated animals.

Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus that causes debilitating arthralgia in humans. Here we describe the development and testing of novel DNA replicon and protein CHIKV vaccine candidates and evaluate their abilities to induce antigen-specific immune responses against CHIKV. We also describe homologous and heterologous prime-boost immunization strategies using novel and previously developed CHIKV vaccine candidates. Immunogenicity and efficacy were studied in a mouse model of CHIKV infection and showed that the DNA replicon and protein antigen were potent vaccine candidates, particularly when used for priming and boosting, respectively. Several prime-boost immunization strategies eliciting unmatched humoral and cellular immune responses were identified. Further characterization by antibody epitope mapping revealed differences in the qualitative immune responses induced by the different vaccine candidates and immunization strategies. Most vaccine modalities resulted in complete protection against wild-type CHIKV infection; however, we did identify circumstances under which certain immunization regimens may lead to enhancement of inflammation upon challenge. These results should help guide the design of CHIKV vaccine studies and will form the basis for further preclinical and clinical evaluation of these vaccine candidates.IMPORTANCE As of today, there is no licensed vaccine to prevent CHIKV infection. In considering potential new vaccine candidates, a vaccine that could raise long-term protective immunity after a single immunization would be preferable. While humoral immunity seems to be central for protection against CHIKV infection, we do not yet fully understand the correlates of protection. Therefore, in the absence of a functional vaccine, there is a need to evaluate a number of different candidates, assessing their merits when they are used either in a single immunization or in a homologous or heterologous prime-boost modality. Here we show that while single immunization with various vaccine candidates results in potent responses, combined approaches significantly enhance responses, suggesting that such approaches need to be considered in the further development of an efficacious CHIKV vaccine.

Peste des petits ruminants virus (PPRV) is a morbillivirus that can cause severe disease in sheep and goats, characterised by pyrexia, pneumo-enteritis, and gastritis. The socio-economic burden of the disease is increasing in underdeveloped countries, with poor livestock keepers being affected the most. Current vaccines consist of cell-culture attenuated strains of PPRV, which induce a similar antibody profile to that induced by natural infection. Generation of a vaccine that enables differentiation of infected from vaccinated animals (DIVA) would benefit PPR control and eradication programmes, particularly in the later stages of an eradication campaign and for countries where the disease is not endemic. In order to create a vaccine that would enable infected animals to be distinguished from vaccinated ones (DIVA vaccine), we have evaluated the immunogenicity of recombinant fowlpox (FP) and replication-defective recombinant human adenovirus 5 (Ad), expressing PPRV F and H proteins, in goats. The Ad constructs induced higher levels of virus-specific and neutralising antibodies, and primed greater numbers of CD8+ T cells than the FP-vectored vaccines. Importantly, a single dose of Ad-H, with or without the addition of Ad expressing ovine granulocyte macrophage colony-stimulating factor and/or ovine interleukin-2, not only induced strong antibody and cell-mediated immunity but also completely protected goats against challenge with virulent PPRV, 4months after vaccination. Replication-defective Ad-H therefore offers the possibility of an effective DIVA vaccine.

The International Committee on Taxonomy of Viruses is a committee of Virology Division of the International Union of Microbiological Societies, and its operation is governed by Statutes agreed with Virology Division. The classification and nomenclature of viruses is then subject to rules formalized into a Code (required by Statute 8.1). The need for a review of the Statutes and Code became clear during editorial work involved in production of the Ninth ICTV Report. Changes to these documents require the approval of the ICTV Executive Committee (EC) and the full ICTV membership. Changes to the Statutes also require the agreement of Virology Division. The changes to the Statutes described in this article were discussed and agreed by the ICTV EC over a period of more than two years. Many of these changes are relatively minor adaptations and clarifications. Notification of a ballot was sent to the 165 members of ICTV. Members were then requested to vote on whether or not to ratify the proposals. The return rate of votes was approximately 41 %, and all proposed changes were accepted unanimously. The proposed changes to the Statutes were then submitted to Virology Division and were approved unanimously by the Advisory Board and Executive Committee on 19 April 2013. In this article, we present the new version of the Statutes, highlighted in bold to show those parts that have recently been changed. Those changes are then explained in the sections that follow. The changes to the Code are the subject of a separate article.