A synthetic human cytomegalovirus pp65-IE1 fusion antigen efficiently induces and expands virus specific T cells.

Infection with human cytomegalovirus (HCMV) can cause severe complications in newborns and immunocompromised patients, and a prophylactic or therapeutic vaccine against HCMV is not available. Here, we generated a HCMV vaccine candidate fulfilling the regulatory requirements for GMP-compliant production and clinical testing. A novel synthetic fusion gene consisting of the coding sequences of HCMV pp65 and IE1 having a deleted nuclear localization sequence and STAT2 binding domain was introduced into the genome of the attenuated vaccinia virus strain MVA.

Critical role of perforin-dependent CD8+ T cell immunity for rapid protective vaccination in a murine model for human smallpox.

Vaccination is highly effective in preventing various infectious diseases, whereas the constant threat of new emerging pathogens necessitates the development of innovative vaccination principles that also confer rapid protection in a case of emergency. Although increasing evidence points to T cell immunity playing a critical role in vaccination against viral diseases, vaccine efficacy is mostly associated with the induction of antibody responses. Here we analyze the immunological mechanism(s) of rapidly protective vaccinia virus immunization using mousepox as surrogate model for human smallpox.

N1L is an ectromelia virus virulence factor and essential for in vivo spread upon respiratory infection.

The emergence of zoonotic orthopoxvirus infections and the threat of possible intentional release of pathogenic orthopoxviruses have stimulated renewed interest in understanding orthopoxvirus infections and the resulting diseases. Ectromelia virus (ECTV), the causative agent of mousepox, offers an excellent model system to study an orthopoxvirus infection in its natural host. Here, we investigated the role of the vaccinia virus ortholog N1L in ECTV infection.

Uptake of antigens from modified vaccinia Ankara virus-infected leukocytes enhances the immunostimulatory capacity of dendritic cells.

Background Aims: Modified vaccinia Ankara (MVA) is a promising vaccine vector for infectious diseases and malignancies. It is fundamental to ascertain its tropism in human leukocyte populations and immunostimulatory mechanisms for application in immunotherapy.

Methods: Human peripheral blood mononuclear cells (PBMC) and leukocyte subpopulations [monocyte-derived dendritic cells (DC), monocytes and B cells] were infected with MVA in order to evaluate their infection rate, changes in surface markers, cytokine expression and apoptosis.

CD40 ligand-triggered human dendritic cells mount interleukin-23 responses that are further enhanced by danger signals.

Interleukin (IL)-23 is a heterodimeric cytokine composed of the IL-23-specific subunit p19 and the p40 subunit which also constitutes part of IL-12. IL-23 propagates development of Th17 cells, a novel T cell subset which produces IL-17 but no interferon-gamma or IL-4. For both, IL-23 and IL-23-driven IL-17, a crucial role in autoimmune diseases such as experimental autoimmune encephalomyelitis, collagen-induced arthritis, and colitis is well accepted.

Induced bronchus-associated lymphoid tissue serves as a general priming site for T cells and is maintained by dendritic cells.

Mucosal vaccination via the respiratory tract can elicit protective immunity in animal infection models, but the underlying mechanisms are still poorly understood. We show that a single intranasal application of the replication-deficient modified vaccinia virus Ankara, which is widely used as a recombinant vaccination vector, results in prominent induction of bronchus-associated lymphoid tissue (BALT). Although initial peribronchiolar infiltrations, characterized by the presence of dendritic cells (DCs) and few lymphocytes, can be found 4 d after virus application, organized lymphoid structures with segregated B and T cell zones are first observed at day 8.

MVA-based H5N1 vaccine affords cross-clade protection in mice against influenza A/H5N1 viruses at low doses and after single immunization.

Human infections with highly pathogenic avian influenza viruses of the H5N1 subtype, frequently reported since 2003, result in high morbidity and mortality. It is feared that these viruses become pandemic, therefore the development of safe and effective vaccines is desirable. MVA-based H5N1 vaccines already proved to be effective when two immunizations with high doses were used.

Preclinical evaluation of a modified vaccinia virus Ankara (MVA)-based vaccine against influenza A/H5N1 viruses.

Highly pathogenic avian influenza viruses of the H5N1 subtype are responsible for an increasing number of infections in humans since 2003. More than 60% of the infections is lethal and new infections are reported frequently. In the light of the pandemic threat caused by these events the rapid availability of safe and effective vaccines is desirable.

Modified vaccinia virus ankara triggers chemotaxis of monocytes and early respiratory immigration of leukocytes by induction of CCL2 expression.

Orthopoxviruses commonly enter into humans and animals via the respiratory tract. Herein, we show that immigration of leukocytes into the lung is triggered via intranasal infection of mice with modified vaccinia virus Ankara (MVA) and not with the vaccinia virus (VACV) Elstree, Wyeth, or Western Reserve (WR) strain. Immigrating cells were identified as monocytes, neutrophils, and CD4(+) lymphocytes by flow cytometry and could be detected 24 h and 48 h postinfection.

Recombinant modified vaccinia virus Ankara expressing the hemagglutinin gene confers protection against homologous and heterologous H5N1 influenza virus infections in macaques.

Background: Highly pathogenic avian influenza viruses of the H5N1 subtype have been responsible for an increasing number of infections in humans since 2003. More than 60% of infected individuals die, and new infections are reported frequently. In light of the pandemic threat caused by these events, the rapid availability of safe and effective vaccines is desirable.

Postexposure immunization with modified vaccinia virus Ankara or conventional Lister vaccine provides solid protection in a murine model of human smallpox.

Background: Decades after the cessation of smallpox vaccination, the potential of the deliberate release of pathogenic orthopoxviruses has forced a reconsideration of using these extremely efficient human vaccines. Scenarios of sudden biothreats have prompted demand for rapidly protective vaccination. However, the feasibility of short-term vaccination (i.

Vaccination with a Modified Vaccinia Virus Ankara-based vaccine protects mice from allergic sensitization.

Background: Currently, no treatment is available for food allergy and strict avoidance of the allergenic food remains the only way to manage the allergy. New strategies leading to a safe and efficacious food allergy treatment are required. Modified vaccinia virus Ankara (MVA), which allows high levels of expression of recombinant protein in vivo and gives rise to a Th1-biased specific immune response, was used as a prophylactic vaccine in a murine model of ovalbumin (OVA) allergy.

Protective efficacy of several vaccines against highly pathogenic H5N1 avian influenza virus under experimental conditions.

Although several vaccines have been developed to protect against highly pathogenic avian influenza of subtype H5N1 'Asia' their efficiency has primarily been assessed individually. Thus, a direct comparison of their performance is still lacking. The following study was conducted to compare the protective efficacy of three commercially available inactivated vaccines based on influenza virus strains of subtypes H5N2 (vaccine A), H5N9 (vaccine B), and H5N3 (vaccine C), as well as two hemagglutinin expressing experimental vector vaccines (modified vaccinia virus Ankara-H5 and Newcastle disease virus-H5) against a lethal dose of highly pathogenic H5N1 avian influenza virus in chickens.

Vaccination with recombinant modified vaccinia virus Ankara expressing bovine respiratory syncytial virus (bRSV) proteins protects calves against RSV challenge.

Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and calves. Bovine RSV (bRSV) is a natural pathogen for cattle, and bRSV infection in calves shares many features with the human infection. Thus, bRSV infection in cattle provides the ideal setting to evaluate the safety and efficacy of novel RSV vaccine strategies.

Recombinant modified vaccinia virus Ankara-based vaccine induces protective immunity in mice against infection with influenza virus H5N1.

Since 2003, the number of human cases of infections with highly pathogenic avian influenza viruses of the H5N1 subtype is still increasing, and, therefore, the development of safe and effective vaccines is considered a priority. However, the global production capacity of conventional vaccines is limited and insufficient for a worldwide vaccination campaign. In the present study, an alternative H5N1 vaccine candidate based on the replication-deficient modified vaccinia virus Ankara (MVA) was evaluated.

Vaccinia virus replication is not affected by APOBEC3 family members.

Background: The APOBEC3G protein represents a novel innate defense mechanism against retroviral infection. It facilitates the deamination of the cytosine residues in the single stranded cDNA intermediate during early steps of retroviral infection. Most poxvirus genomes are relatively A/T-rich, which may indicate APOBEC3G-induced mutational pressure.

Short-term, but not post-exposure, protection against lethal orthopoxvirus challenge after immunization with modified vaccinia virus Ankara.

Safety-tested vaccinia virus (VACV) MVA serves as a candidate third-generation vaccine against smallpox. Here, MVA immunization of mice shortly before or after lethal respiratory challenge with VACV Western Reserve was investigated. Whilst post-exposure treatment failed to protect animals, immunizations on day 2 prior to challenge were fully protective.

Double-stranded RNA-binding protein E3 controls translation of viral intermediate RNA, marking an essential step in the life cycle of modified vaccinia virus Ankara.

Infection of human cells with modified vaccinia virus Ankara (MVA) activates the typical cascade-like pattern of viral early-, intermediate- and late-gene expression. In contrast, infection of human HeLa cells with MVA deleted of the E3L gene (MVA-DeltaE3L) results in high-level synthesis of intermediate RNA, but lacks viral late transcription. The viral E3 protein is thought to bind double-stranded RNA (dsRNA) and to act as an inhibitor of dsRNA-activated 2'-5'-oligoadenylate synthetase (2'-5'OA synthetase)/RNase L and protein kinase (PKR).

Protective and disease-enhancing immune responses induced by recombinant modified vaccinia Ankara (MVA) expressing respiratory syncytial virus proteins.

Modified vaccinia Ankara (MVA) recombinants expressing single or multiple RSV surface proteins (F or G) are promising potential vaccines. We studied humoral and cellular responses induced by MVA-F and MVA-G in mice, comparing them to a formalin inactivated RSV preparation (FI-RSV) known to increase disease severity. MVA-F or MVA-G vaccination enhanced weight loss during RSV challenge, but did not show the lung eosinophilia seen after FI-RSV vaccination.