TY  - JOUR
AB  - Introduction: Invasive meningococcal disease (IMD) is a severe disease mainly affecting infants and young children. The most common serogroup causing IMD in Germany is the serogroup type B Neisseria meningitidis (MenB). The aim of the present study is to estimate the economic burden of MenB-related IMD in Germany.Method: A bottom-up, model-based costing approach has been used to calculate the diagnose- and age-specific yearly lifetime costs of a hypothetical cohort of MenB-related IMD cases. Direct costs contain the treatment cost for the acute phase of the disease, long-term sequelae, costs for rehabilitation, and public health response. Indirect costs are calculated for the human-capital approach and the friction-cost approach considering productivity losses of patients or parents for the acute phase and long-term sequelae. Publicly available databases from the Federal Statistical Office, the SOEP panel data set, literature, and expert opinion were used as data sources. All future costs beyond the reference year of 2015 were discounted at 3%.Results: The total costs for the hypothetical cohort (343 patients) from a societal perspective are (sic)19.6 million ((sic)57,100/IMD case) using the friction-cost approach and (sic)58.8 million ((sic)171,000/IMD case) using the human-capital approach. Direct costs amount to (sic)18.6 million or (sic)54,300 (sic)/case. Sequelae are responsible for 81% of the direct costs/case.Discussion: The elevated costs/MenB-related IMD case reflect the severity of the disease. The total costs are sensitive to the productivity-loss estimation approach applied. MenB is an uncommon but severe disease; The costs/case reflect the severity of the disease and is within the same magnitude as for human papilloma virus infections. The available literature on sequelae is due to the uncommonness limited and heterogeneous. (C) 2019 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.
AU  - Scholz, S.*
AU  - Koerber, F.
AU  - Meszaros, K.*
AU  - Fassbender, R.M.*
AU  - Ultsch, B.*
AU  - Welte, R.R.*
AU  - Greiner, W.*
C1  - 55306
C2  - 46334
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
SP  - 1692-1701
TI  - The cost-of-illness for invasive meningococcal disease caused by serogroup B Neisseria meningitidis (MenB) in Germany.
JO  - Vaccine
VL  - 37
IS  - 12
PB  - Elsevier Sci Ltd
PY  - 2019
SN  - 0264-410X
ER  - 

TY  - JOUR
AB  - More than 50% of the world's population is infected with the bacterium Helicobacter pylori. If left untreated, infection with H. pylori can cause chronic gastritis and peptic ulcer disease, which may progress into gastric cancer. Owing to the limited efficacy of anti-H. pylori antibiotic therapy in clinical practice, the development of a protective vaccine to combat this pathogen has been a tempting goal for several years. In this study, a chimeric gene coding for the antigenic parts of H. pylori FIiD, UreB, VacA, and CagL was generated and expressed in bacteria and the potential of the resulting fusion protein (rFUVL) to induce humoral and cellular immune responses and to provide protection against H. pylori infection was evaluated in mice. Three different immunization adjuvants were tested along with rFUVL: CpG oligodeoxynucleotides (CpG ODN), Addavax, and Cholera toxin subunit B. Compared to the control group that had received PBS, vaccinated mice showed significantly higher cellular recall responses and antigen-specific IgG2a, IgG1, and gastric IgA antibody titers. Importantly, rFUVL immunized mice exhibited a reduction of about three orders of magnitude in their stomach bacterial loads. Thus, adjuvanted rFUVL might be considered as a promising vaccine candidate for the control of H. pylori infection.
AU  - Ghasemi, A.*
AU  - Mohammad, N.*
AU  - Mautner, J.
AU  - Taghipour Karsabet, M.*
AU  - Amani, J.*
AU  - Ardjmand, A.*
AU  - Vakili, Z.*
C1  - 54000
C2  - 45193
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
SP  - 5124-5132
TI  - Immunization with a recombinant fusion protein protects mice against Helicobacter pylori infection.
JO  - Vaccine
VL  - 36
IS  - 34
PB  - Elsevier Sci Ltd
PY  - 2018
SN  - 0264-410X
ER  - 

TY  - JOUR
AB  - AIMS/HYPOTHESIS: Vaccinations in early childhood potentially stimulate the immune system and may thus be relevant for the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D). We determined the association of vaccination burden with T1D-associated islet autoimmunity in children with high familial risk followed prospectively from birth. METHODS: A total of 20,570 certified vaccination records from 1918 children were correlated with time to onset of T1D-associated islet autoimmunity using Cox regression, considering multiple time periods up until age two years and vaccination types, and adjusting for HLA genotype, sex, delivery mode, season of birth, preterm delivery and maternal T1D status. Additionally, prospective claims data of 295,420 subjects were used to validate associations for the tick-borne encephalitis (TBE) vaccination. RESULTS: Most vaccinations were not associated with a significantly increased hazard ratio (HR) for islet autoimmunity (e.g. HR [95% confidence interval]: 1.08 [0.96-1.21] per additional vaccination against measles, mumps and rubella at age 0-24months). TBE vaccinations within the first two years of life were nominally associated with a significantly increased autoimmunity risk (HR: 1.44 [1.06-1.96] per additional vaccination at age 0-24months), but this could not be confirmed with respect to outcome T1D in the validation cohort (HR: 1.02 [0.90-1.16]). CONCLUSIONS: We found no evidence that early vaccinations increase the risk of T1D-associated islet autoimmunity development. The potential association with early TBE vaccinations could not be confirmed in an independent cohort and appears to be a false positive finding.
AU  - Beyerlein, A.
AU  - Strobl, A.N.*
AU  - Winkler, C.
AU  - Carpus, M.
AU  - Knopff, A.
AU  - Donnachie, E.*
AU  - Ankerst, D.P.*
AU  - Ziegler, A.-G.
C1  - 50611
C2  - 42532
CY  - Oxford
SP  - 1735-1741
TI  - Vaccinations in early life are not associated with development of islet autoimmunity in type 1 diabetes high-risk children: Results from prospective cohort data.
JO  - Vaccine
VL  - 35
IS  - 14
PB  - Elsevier Sci Ltd
PY  - 2017
SN  - 0264-410X
ER  - 

TY  - JOUR
AB  - 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. This recombinant MVA, MVA-syn65_IE1, allowed for the production of a stable ∼120kDa syn65_IE1 fusion protein upon tissue culture infection. MVA-syn65_IE1 infected CD40-activated B cells activated and expanded pp65- and IE1-specific T cells derived from HCMV-seropositive donors to at least equal levels as control recombinant MVA expressing single genes for pp65 or IE1. Additionally, we show that MVA-syn65_IE1 induced HCMV pp65- and IE1-epitope specific T cells in HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice. Thus, MVA-syn65_IE1 represents a promising vaccine candidate against HCMV and constitutes a basis for the generation of a multivalent vaccine targeting relevant pathogens in immunocompromised patients.
AU  - Link, E.K.*
AU  - Brandmüller, C.*
AU  - Suezer, Y.*
AU  - Ameres, S.
AU  - Volz, A.*
AU  - Moosmann, A.
AU  - Sutter, G.*
AU  - Lehmann, M.H.*
C1  - 51733
C2  - 43460
CY  - Oxford
SP  - 5131-5139
TI  - A synthetic human cytomegalovirus pp65-IE1 fusion antigen efficiently induces and expands virus specific T cells.
JO  - Vaccine
VL  - 35
IS  - 8
PB  - Elsevier Sci Ltd
PY  - 2017
SN  - 0264-410X
ER  - 

TY  - JOUR
AB  - BACKGROUND: Therapeutic vaccination is a novel treatment approach for chronic hepatitis B, but only had limited success so far. We hypothesized that optimized vaccination schemes have increased immunogenicity, and aimed at increasing therapeutic hepatitis B vaccine efficacy. METHODS: Modified Vaccinia virus Ankara (MVA) expressing hepatitis B virus (HBV) antigens was used to boost protein-prime vaccinations in wildtype and HBV-transgenic (HBVtg) mice. RESULTS: Protein-prime/MVA-boost vaccination was able to overcome HBV-specific tolerance in HBVtg mice with low and medium but not with high antigenemia. HBV-specific antibody titers, CD8+ T-cell frequencies and polyfunctionality inversely correlated with HBV antigen levels. However, optimization of the adjuvant formulation, increasing the level of antigen expression and utilization of HBsAg of heterologous subtype induced HBV-specific CD8+ and CD4+ T-cells and neutralizing antibodies even in high-antigenemic HBVtg mice. CONCLUSIONS: Our results indicate that high HBV antigen levels limit the immunological responsiveness to therapeutic vaccination but optimization of the vaccine formulation can overcome tolerance even in the presence of high antigenemia. These findings have important implications for the development of future therapeutic hepatitis B vaccination strategies and potentially also for the stratification of chronic hepatitis B patients for therapeutic vaccination.
AU  - Backes, S.
AU  - Jager, C.
AU  - Dembek, C.J.
AU  - Kosinska, A.
AU  - Bauer, T.
AU  - Stephan, A.-S.
AU  - Dišlers, A.*
AU  - Mutwiri, G.*
AU  - Busch, D.H.
AU  - Babiuk, L.A.*
AU  - Gasteiger, G.
AU  - Protzer, U.
C1  - 47704
C2  - 39562
CY  - Oxford
SP  - 923-932
TI  - Protein-prime/modified vaccinia virus Ankara vector-boost vaccination overcomes tolerance in high-antigenemic HBV-transgenic mice.
JO  - Vaccine
VL  - 34
IS  - 7
PB  - Elsevier Sci Ltd
PY  - 2016
SN  - 0264-410X
ER  - 

TY  - JOUR
AB  - Brucella vaccines consisting of live attenuated Brucella strains are currently used in livestock, but safety concerns preclude their application in humans. Subunit vaccines have recently emerged as safe and efficacious alternatives in both humans and animals. In this study, subunit vaccines were developed that consisted of a recombinant outer membrane protein (rOmp31) and the trigger factor chaperone protein (rTF) of Brucella melitensis, either alone or in combination. BALB/c mice that were immunized with rOmp31+rTF showed comparable but slightly higher TF-specific IgG1 and IgG2a antibodies as compared to mice with rTF alone. Indeed, mice given this combination had titers of rOmp31-specific antibodies similar to those immunized with rOmp31 alone. In lymphocyte reactivation experiments, the splenocytes of immunized mice, whether given either of these antigens alone or as a cocktail, exhibited a strong antigen-specific recall proliferative response and expressed high amounts of IFN-γ, IL-12, IL-10 and IL-6. Both rTF and rTF+rOmp31 vaccinated mice exhibited significantly higher CD4 and CD8 levels compared to the PBS group. The combination of rOmp31 and rTF provided protection against B. melitensis infection comparable to that of vaccine strain Rev.1. In comparison to rTF alone, combination of rTF and rOmp31 caused only a slight increase in protection level. Although combination of rTF and rOmp31 caused a non-significant increase in IFN-γ induction, antibody level, proliferation index and CD4 and CD8 frequencies compared to rTF alone, its cumulative effects on aforesaid parameters may be viewed as a better efficacy.
AU  - Ghasemi, A.*
AU  - Jeddi-Tehrani, M.*
AU  - Mautner, J.
AU  - Salari, M.H.*
AU  - Zarnani, A.H.*
C1  - 46970
C2  - 39094
SP  - 5532-5538
TI  - Simultaneous immunization of mice with Omp31 and TF provides protection against Brucella melitensis infection.
JO  - Vaccine
VL  - 33
IS  - 42
PY  - 2015
SN  - 0264-410X
ER  - 

TY  - JOUR
AB  - Brucella spp. are zoonotic Gram-negative intracellular pathogens with the ability to survive and replicate in phagocytes. It has been shown that bacterial proteins expressed abundantly in this niche are stress-related proteins capable of triggering effective immune responses. BMEI1549 is a molecular chaperone designated DnaK that is expressed under stress conditions and helps to prevent formation of protein aggregates. In order to study the potential of DnaK as a prospective Brucella subunit vaccine, immunogenicity and protective efficacy of recombinant DnaK from Brucella melitensis was evaluated in BALB/c mice. The dnak gene was cloned, expressed in Escherichia coli, and the resulting recombinant protein used as subunit vaccine. DnaK-immunized mice showed a strong lymphocyte proliferative response to in vitro antigen stimulation. Although comparable levels of antigen-specific IgG2a and IgG1 were observed in immunized mice, high amounts of IFN-γ, IL-12 and IL-6, no detectable level of IL-4 and very low levels of IL-10 and IL-5 were produced by splenocytes of vaccinated mice suggesting induction of a Th1 dominant immune response by DnaK. Compared to control animals, mice vaccinated with DnaK exhibited a significant degree of protection against subsequent Brucella infection (p<0.001), albeit this protection was less than the protection conferred by Rev.1 (p<0.05). A further increase in protection was observed, when DnaK was combined with recombinant Omp31. Notably, this combination, as opposed to each component alone, induced statistically similar level of protection as induced by Rev.1 suggesting that DnaK could be viewed as a promising candidate for the development of a subunit vaccine against brucellosis.
AU  - Ghasemi, A.*
AU  - Jeddi-Tehrani, M.*
AU  - Mautner, J.
AU  - Salari, M.H.*
AU  - Zarnani, A.H.*
C1  - 32346
C2  - 35009
SP  - 6659-6666
TI  - Immunization of mice with a novel recombinant molecular chaperon confers protection against Brucella melitensis infection.
JO  - Vaccine
VL  - 32
IS  - 49
PY  - 2014
SN  - 0264-410X
ER  - 

TY  - JOUR
AB  - BACKGROUND: Following vaccination with traditional smallpox vaccines or after exposure to vaccinated individuals, subjects with atopic dermatitis (AD) can develop eczema vaccinatum, a severe disease with disseminated eruption of pustular contagious lesions. Alternative smallpox vaccines with an improved safety profile would address this unmet medical need. METHODS: An open-label controlled Phase I clinical trial was conducted to investigate the safety and immunogenicity of modified vaccinia Ankara (MVA) in 15 healthy subjects compared to 45 subjects with either mild allergic rhinitis, a history of AD or presenting with mild active AD. MVA was given (Week 0 and 4) by a subcutaneous injection during a 28-week observation period. RESULTS: No serious adverse event was reported and vaccinations with MVA did not lead to any clinically relevant skin reactions in AD subjects. Unsolicited administration site reactions did not show any trends compared to the healthy subject group. The majority of adverse reactions were mild to moderate, and all reactions were transient and resolved without intervention. The majority of vaccinees had seroconverted by ELISA (80-93%) and PRNT (69-79%) already two weeks after the first vaccination, increasing to 100% after the second immunization, with peak GMT above 1000 and 145 for ELISA and PRNT, respectively. CONCLUSIONS: MVA was equally well tolerated and immunogenic in all enrolled subjects with mild to moderate pain and redness at the injection site being the most frequent adverse reactions. There were no differences in the safety or immunogenicity profile of MVA in healthy subjects or those with AD or allergic rhinitis. The study has confirmed MVA as a promising smallpox vaccine candidate and demonstrated in a small study population that the vaccine has a similar safety and immunogenicity profile in healthy subjects and people with active AD. Clinical trials registration: NCT00189917.
AU  - von Sonnenburg, F.*
AU  - Perona, P.*
AU  - Darsow, U.
AU  - Ring, J.
AU  - von Krempelhuber, A.*
AU  - Vollmar, J.*
AU  - Roesch, S.*
AU  - Baedeker, N.*
AU  - Kollaritsch, H.*
AU  - Chaplin, P.*
C1  - 31999
C2  - 34929
SP  - 5696-5702
TI  - Safety and immunogenicity of modified vaccinia Ankara as a smallpox vaccine in people with atopic dermatitis.
JO  - Vaccine
VL  - 32
IS  - 43
PY  - 2014
SN  - 0264-410X
ER  - 

TY  - JOUR
AB  - Therapeutic vaccines are currently being developed for chronic hepatitis B and C. As an alternative to long-term antiviral treatment or to support only partially effective therapy, they should activate the patient's immune system effectively to fight and finally control the virus. A paradigm of therapeutic vaccination is the potent induction of T-cell responses against key viral antigens - besides activation of a humoral immune response. We have evaluated the potential of a novel vaccine formulation comprising particulate hepatitis B surface (HBsAg) and core antigen (HBcAg), and the saponin-based ISCOMATRIX (TM) adjuvant for its ability to stimulate T and B cell responses in C57BL/6 mice and its ability to break tolerance in syngeneic HBV transgenic (HBVtg) mice. In C57BL/6 mice, the vaccine induced multifunctional HBsAg- and HBcAg-specific CD8+ T cells detected by staining for IFN gamma, TNF alpha and IL-2, as well as high antibody titers against both antigens. Vaccination of HBVtg animals induced potent HBsAg- and HBcAg-specific CD8+ T-cell responses in spleens and HBcAg-specific CD8+ T-cell responses in livers as well as anti-HBs seroconversion two weeks post injection. Vaccination further reduced HBcAg expression in livers of HBVtg mice without causing liver damage. In summary, this study demonstrates therapeutic efficacy of a novel vaccine formulation in a mouse model of immunotolerant, chronic HBV infection.
AU  - Buchmann, P.*
AU  - Dembek, C.J.
AU  - Kuklick, L.*
AU  - Jager, C.*
AU  - Tedjokusumo, R.
AU  - von Freyend, M.J.*
AU  - Drebber, U.*
AU  - Janowicz, Z.*
AU  - Melber, K.*
AU  - Protzer, U.
C1  - 23526
C2  - 31207
SP  - 1197-1203
TI  - A novel therapeutic hepatitis B vaccine induces cellular and humoral immune responses and breaks tolerance in Hepatitis B Virus (HBV) transgenic mice.
JO  - Vaccine
VL  - 31
IS  - 8
PB  - Elsevier Sci.
PY  - 2013
SN  - 0264-410X
ER  - 

TY  - JOUR
AB  - In chronic Hepatitis B Virus (HBV) infection the function of dendritic cells (DC), T- and B-cells is impaired. DC vaccination is an option to overcome this. DC pulsed in vitro with HBV sub viral particles (HBVsvp) and used to immunize mice can activate HBV directed humoral and cellular immune responses. In the present study we vaccinated HBV transgenic mice as a model for chronic HBV infection and observed humoral and cellular immune responses. In these mice, the lacking immune response against HBV is mainly due to peripheral tolerance. HBVsvp, together with LPS as a co-activating molecule, were used for pulsing and in vitro activation of DC. HBV transgenic mice were injected with pulsed DC two times. Four weeks after DC vaccination humoral and cellular immune responses, viral antigen levels and liver histology were analyzed. DC vaccinated HBV-transgenic mice developed a strong HBV specific antibody and T-cell response after DC vaccination. Neither circulating HBV antigen levels nor viremia, however, were controlled. No liver damage was observed. These results demonstrate that in vitro activation of DC and loading with HBVsvp can overcome tolerance against HBV and reactivate B- and T-cell responses in HBV transgenic mice, but were not sufficient to lead to virus control in these mice. Vaccination using DC, the key players of cellular and humoral immunity, after in vitro reactivation promises to break tolerance against HBV and may help patients with chronic hepatitis B to clear the infection.
AU  - Farag, M.M.S.*
AU  - Tedjokusumo, R.
AU  - Flechtenmacher, C.*
AU  - Asen, T.
AU  - Stremmel, W.*
AU  - Müller, M.*
AU  - Protzer, U.
AU  - Weigand, K.*
C1  - 10627
C2  - 30338
SP  - 6034-6039
TI  - Immune tolerance against HBV can be overcome in HBV transgenic mice by immunization with dendritic cells pulsed by HBVsvp.
JO  - Vaccine
VL  - 30
IS  - 42
PB  - Elsevier
PY  - 2012
SN  - 0264-410X
ER  - 

TY  - JOUR
AB  - Dendritic cells phagocytose pathogens leading to maturation and cross-presentation on MHC class I. We found that the efficiency of cross-priming in mice after vaccination with biodegradable poly(D,L-lactide-co-glycolide) microspheres (MSs) was enhanced when ovalbumin was coencapsulated together with either a CpG oligonucleotide or polyI:C as compared to co-inoculation of ovalbumin-bearing MS with soluble or separately encapsulated adjuvants. A single immunization with MS containing coencaspsulated CpG and ovalbumin yielded 9% SIINFEKL/H-2K(b) tetramer positive CTLs, production of IFN-gamma, efficient cytolysis, and protection from vaccinia virus infection. Taken together, coencapsulation of adjuvant and antigen is an important paradigm for the generation of potent CTL responses.
AU  - Schlosser, E.*
AU  - Mueller, M.*
AU  - Fischer, S.*
AU  - Basta, S.*
AU  - Busch, D.H.
AU  - Gander, B.*
AU  - Groettrup, M.*
C1  - 4895
C2  - 25471
SP  - 1626-1637
TI  - TLR ligands and antigen need to be coencapsulated into the same biodegradable microsphere for the generation of potent cytotoxic T lymphocyte responses.
JO  - Vaccine
VL  - 26
IS  - 13
PB  - Elsevier
PY  - 2008
SN  - 0264-410X
ER  - 

TY  - JOUR
AB  - Severe acute respiratory syndrome (SARS) is a Serious infectious disease Caused by the SARS coronavirus. We assessed the potential of prime-boost vaccination protocols based oil the nucleocapsid (NC) protein co-administered with a derivative of the mucosal adjuvant MALP-2 or expressed by modified Vaccinia virus Ankara (MVA-NC) to stimulate humoral and cellular immune responses at systemic and mucosal levels. The obtained results demonstrated that strong immune responses can be elicited both at systemic and mucosal levels following a heterologous prime-boost vaccination protocol consisting in pruning with NC protein add-mixed with MALP-2 by intranasal route and boosting with MVA-NC by intramuscular route.
AU  - Schulze, K.*
AU  - Staib, C.
AU  - Schatzl, H.M.*
AU  - Ebensen, T.*
AU  - Erfle, V.
AU  - Guzman, C.A.*
C1  - 3003
C2  - 25932
SP  - 6678-6684
TI  - A prime-boost vaccination protocol optimizes immune responses against the nucleocapsid protein of the SARS coronavirus.
JO  - Vaccine
VL  - 26
IS  - 51
PB  - Elsevier
PY  - 2008
SN  - 0264-410X
ER  - 

TY  - JOUR
AB  - 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. Here, we have evaluated the efficacy and safety of modified vaccinia virus Ankara (rMVA)-based vaccine candidates, expressing the bovine RSV-F protein, either or not in combination with the G protein, in colostrums-deprived SPF calves born by caesarean section. Vaccination induced bRSV-specific IgG and CD8 T cell responses. Importantly, no IgE responses were detected. After bRSV challenge, rMVA vaccinated calves experienced less severe symptoms of lower respiratory tract disease compared to the mock-immunized control group. Immunized animals showed reduced pulmonary virus loads, and no eosinophilic infiltration or enhanced respiratory distress. In conclusion, candidate rMVA/bRSV vaccines induced protective and safe immune responses in calves.
AU  - Antonis, A.F.G.*
AU  - van der Most, R.G.*
AU  - Suezer, Y.*
AU  - Stockhofe-Zurwieden, N.*
AU  - Daus, F.*
AU  - Sutter, G.
AU  - Schrijver, R.S.*
C1  - 5558
C2  - 28295
SP  - 4818-4827
TI  - Vaccination with recombinant modified vaccinia virus Ankara expressing bovine respiratory syncytial virus (bRSV) proteins protects calves against RSV challenge.
JO  - Vaccine
VL  - 25
IS  - 25
PB  - Elsevier
PY  - 2007
SN  - 0264-410X
ER  - 

TY  - JOUR
AB  - Efficient vaccines against AIDS, Hepatitis C and other persistent virus infections are urgently needed. Vaccine development has been especially hampered by the lack of suitable small animal models to reliably test the protective capacity of candidate vaccines against such chronic viral infections. A natural mouse pathogen such as MHV-68 that persists lifelong after infection, appears to be a particularly promising candidate for a more relevant model system. Here, we investigated infections with recombinant MHV-68 as novel mouse challenge model to test the efficacy of heterologous vaccines based on recombinant modified vaccinia virus Ankara (MVA). To apply ovalbumin (OVA) as a model antigen, we constructed the recombinant virus MHV-68-OVA by BAC technology and characterized genetic stability and replicative capacity of the virus in vitro and in vivo. We demonstrated the ability of MHV-68-OVA to produce ovalbumin upon tissue culture infection. Moreover, the use of MHV-68-OVA-infected target cells allowed for efficient ex vivo amplification of OVA-specific, MHC class I-restricted CD8 T cells derived from MVA-OVA-vaccinated C57BL/6 mice. Finally, we immunized C57BL/6 mice with MVA-OVA and challenged the animals with MHV-68-OVA testing different time points and routes of infection. Vaccinated mice were infected with MHV-68-OVA but showed reduced viral loads in the acute and latent phase of challenge infection. These data strongly suggest the usefulness of the MHV-68 challenge model for further evaluation of recombinant vaccines against persisting virus infections.
AU  - El-Gogo, S.*
AU  - Staib, C.*
AU  - Meyr, M.*
AU  - Erfle, V.
AU  - Sutter, G.
AU  - Adler, H.
C1  - 4182
C2  - 24337
SP  - 3934-3945
TI  - Recombinant murine gammaherpesvirus 68 (MHV-68) as challenge virus to test efficacy of vaccination against chronic virus infections in the mouse model.
JO  - Vaccine
VL  - 25
IS  - 20
PB  - Elsevier
PY  - 2007
SN  - 0264-410X
ER  - 

TY  - JOUR
AU  - Meyer, P.
AU  - Menzel, M.
AU  - Muellinger, B.*
AU  - Weber, N.
AU  - Haeussinger, K.
AU  - Ziegler-Heitbrock, L.
C1  - 4936
C2  - 23897
SP  - 5832-5838
TI  - Inhalative vaccination with pneumococcal polysaccharide in patients with chronic obstructive pulmonary disease.
JO  - Vaccine
VL  - 24
PY  - 2006
SN  - 0264-410X
ER  - 

TY  - JOUR
AU  - Menzel, M.*
AU  - Muellinger, B.*
AU  - Weber, N.
AU  - Häussinger, K.
AU  - Ziegler-Heitbrock, L.
C1  - 1004
C2  - 23072
SP  - 5113-5119
TI  - Inhalative vaccination with pneumococcal polysaccharide in healthy volunteers.
JO  - Vaccine
VL  - 23
PY  - 2005
SN  - 0264-410X
ER  - 

TY  - JOUR
AU  - Olszewska, W.*
AU  - Suezer, Y.
AU  - Openshaw, P.J.M.*
C1  - 3045
C2  - 22425
SP  - 215-221
TI  - Protective and disease-enhancing immune responses induced by recombinant modified vaccinia Ankara (MVA) expressing respiratory syncytial virus proteins.
JO  - Vaccine
VL  - 23
PY  - 2004
SN  - 0264-410X
ER  - 

TY  - JOUR
AU  - Welte, R.
AU  - van den Dobbelsteen, G.*
AU  - Bos, J.M.*
AU  - de Melker, H.*
AU  - van Alphen, L.*
AU  - Spanjaard, L.*
AU  - Rümke, H.C.*
AU  - Postma, M.J.*
C1  - 1873
C2  - 22612
SP  - 470-479
TI  - Economic evaluation of meningococcal serogroup C conjugate vaccination programmes in The Netherlands and its impact on decision-making.
JO  - Vaccine
VL  - 23
PY  - 2004
SN  - 0264-410X
ER  - 

TY  - JOUR
AU  - Cosma, A.
AU  - Nagaraj, R.
AU  - Bühler, S.*
AU  - Hinkula, J.*
AU  - Busch, D.H.*
AU  - Sutter, G.
AU  - Goebel, F.D.*
AU  - Erfle, V.
C1  - 9504
C2  - 21302
SP  - 21-29
TI  - Therapeutic vaccination with MVA-HIV-1 nef elicits Nef-specific T-helper cell responses in chronically HIV-1 infected individuals. 
JO  - Vaccine
VL  - 22
PY  - 2003
SN  - 0264-410X
ER  - 

TY  - JOUR
AU  - Stittelaar, K.J.*
AU  - Gruters, R.A.*
AU  - Schutten, M.*
AU  - van Baalen, C.A.*
AU  - van Amerongen, G.*
AU  - Cranage, M.*
AU  - Liljeström, P.*
AU  - Sutter, G.
AU  - Osterhaus, A.D.M.E.*
C1  - 21990
C2  - 20520
SP  - 2921-2927
TI  - Comparison of the efficacy of early versus late viral proteins in vaccination against SIV.
JO  - Vaccine
VL  - 20
PY  - 2002
SN  - 0264-410X
ER  - 

TY  - JOUR
AU  - Nilsson, C.*
AU  - Mäkitalo, B.*
AU  - Berglund, P.*
AU  - Bex, F.*
AU  - Liljeström, P.*
AU  - Sutter, G.
AU  - Erfle, V.
AU  - Ten Haaft, P.*
AU  - Heeney, J.*
AU  - Biberfeld, G.*
AU  - Thorstensson, R.*
C1  - 21903
C2  - 20174
SP  - 3526-3536
TI  - Enhanced simian immunodeficiency virus-specific immune responses in macaques induced by priming with recombinant Semliki Forest virus and boosting with modified vaccinia virus Ankara.
JO  - Vaccine
VL  - 19
PY  - 2001
SN  - 0264-410X
ER  - 

TY  - JOUR
AU  - Collings, A.*
AU  - Pitkänen, J.*
AU  - Strengell, M.*
AU  - Tähtinen, M.*
AU  - Lagerstedt, A.*
AU  - Hakkarainen, K.*
AU  - Ovod, V.*
AU  - Sutter, G.
AU  - Ustav, M.*
AU  - Ustav, E.*
AU  - Männik, A.*
C1  - 21298
C2  - 19413
SP  - 460-467
TI  - Humoral and cellular immune responses to HIV-1 Nev in mice DNA-immunised with non- replicating or self-replicating expression vectors.
JO  - Vaccine
VL  - 18
PY  - 2000
SN  - 0264-410X
ER  - 

TY  - JOUR
AU  - Osterhaus, A.D.*
AU  - van Baalen, C.A.*
AU  - Gruters, R.A.*
AU  - Schutten, M.*
AU  - Siebelink, C.H.J.*
AU  - Hulskotte, E.G.J.*
AU  - Tijhaar, E.J.*
AU  - Randall, R.E.R.*
AU  - van Amerongen, G.*
AU  - Fleuchaus, A.G.
AU  - Erfle, V.
AU  - Sutter, G.
C1  - 21297
C2  - 19412
SP  - 2713-2714
TI  - Vaccination with Rev and Tat against AIDS.
JO  - Vaccine
VL  - 17
PY  - 1999
SN  - 0264-410X
ER  - 

TY  - JOUR
AU  - von Brunn, A.
AU  - Reichhuber, C.
AU  - Brand, M.
AU  - Bechowsky, B.
AU  - Gürtler, L.
AU  - Eberle, J.
AU  - Kleinschmidt, A.
AU  - Erfle, V.
AU  - Schödel, F.
C1  - 20460
C2  - 13668
TI  - The Principal Neutralizing Determinant (V3) of HIV-1 Induces HIV-1-neutralizing Antibodies upon Expression on HBcAg Particles.
JO  - Vaccine
VL  - 93
PY  - 1993
SN  - 0264-410X
ER  -