scholarly journals Safety Profile of the Viral Vectors of Attenuated Fowlpox Strain FP9 and Modified Vaccinia Virus Ankara Recombinant for Either of 2 Preerythrocytic Malaria Antigens, ME-TRAP or the Circumsporozoite Protein, in Children and Adults in Kenya

2006 ◽  
Vol 42 (8) ◽  
pp. 1102-1110 ◽  
Author(s):  
P. Bejon ◽  
N. Peshu ◽  
S. C. Gilbert ◽  
B. S. Lowe ◽  
C. S. Molyneux ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Safety Profile ◽  
Viral Vectors ◽  
Circumsporozoite Protein ◽  
Modified Vaccinia Virus Ankara

scholarly journals Safety, Immunogenicity, and Efficacy of Prime-Boost Immunization with Recombinant Poxvirus FP9 and Modified Vaccinia Virus Ankara Encoding the Full-Length Plasmodium falciparum Circumsporozoite Protein

2006 ◽  
Vol 74 (5) ◽  
pp. 2706-2716 ◽  
Author(s):  
Michael Walther ◽  
Fiona M. Thompson ◽  
Susanna Dunachie ◽  
Sheila Keating ◽  
Stephen Todryk ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Circumsporozoite Protein ◽  
Fowlpox Virus ◽  
Partial Protection ◽  
Modified Vaccinia Virus Ankara ◽  
Boost Immunization ◽  
Recombinant Fowlpox Virus ◽  
First Time

ABSTRACT Heterologous prime-boost immunization with DNA and various recombinant poxviruses encoding malaria antigens is capable of inducing strong cell-mediated immune responses and partial protection in human sporozoite challenges. Here we report a series of trials assessing recombinant fowlpox virus and modified vaccinia virus Ankara encoding the Plasmodium falciparum circumsporozoite protein in various prime-boost combinations, doses, and application routes. For the first time, these vaccines were administered intramuscularly and at doses of up to 5 × 108 PFU. Vaccines containing this antigen proved safe and induced modest immune responses but showed no evidence of efficacy in a sporozoite challenge.

scholarly journals A DNA Prime-Modified Vaccinia Virus Ankara Boost Vaccine Encoding Thrombospondin-Related Adhesion Protein but Not Circumsporozoite Protein Partially Protects Healthy Malaria-Naive Adults against Plasmodium falciparum Sporozoite Challenge

2006 ◽  
Vol 74 (10) ◽  
pp. 5933-5942 ◽  
Author(s):  
S. J. Dunachie ◽  
M. Walther ◽  
J. E. Epstein ◽  
S. Keating ◽  
T. Berthoud ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Vaccinia Virus ◽  
Ex Vivo ◽  
Circumsporozoite Protein ◽  
Elispot Response ◽  
Adhesion Protein ◽  
Modified Vaccinia Virus Ankara ◽  
Boost Vaccine ◽  
Falciparum Sporozoite ◽  
Ifn Γ

ABSTRACT The safety, immunogenicity, and efficacy of DNA and modified vaccinia virus Ankara (MVA) prime-boost regimes were assessed by using either thrombospondin-related adhesion protein (TRAP) with a multiple-epitope string ME (ME-TRAP) or the circumsporozoite protein (CS) of Plasmodium falciparum. Sixteen healthy subjects who never had malaria (malaria-naive subjects) received two priming vaccinations with DNA, followed by one boosting immunization with MVA, with either ME-TRAP or CS as the antigen. Immunogenicity was assessed by ex vivo gamma interferon (IFN-γ) enzyme-linked immunospot assay (ELISPOT) and antibody assay. Two weeks after the final vaccination, the subjects underwent P. falciparum sporozoite challenge, with six unvaccinated controls. The vaccines were well tolerated and immunogenic, with the DDM-ME TRAP regimen producing stronger ex vivo IFN-γ ELISPOT responses than DDM-CS. One of eight subjects receiving the DDM-ME TRAP regimen was completely protected against malaria challenge, with this group as a whole showing significant delay to parasitemia compared to controls (P = 0.045). The peak ex vivo IFN-γ ELISPOT response in this group correlated strongly with the number of days to parasitemia (P = 0.033). No protection was observed in the DDM-CS group. Prime-boost vaccination with DNA and MVA encoding ME-TRAP but not CS resulted in partial protection against P. falciparum sporozoite challenge in the present study.

scholarly journals Recombinant Modified Vaccinia Virus Ankara Generating Ebola Virus-Like Particles

2017 ◽  
Vol 91 (11) ◽  
Author(s):  
Marc Schweneker ◽  
Andrea S. Laimbacher ◽  
Gert Zimmer ◽  
Susanne Wagner ◽  
Elisabeth M. Schraner ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Viral Vectors ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Virus Disease ◽  
Hemorrhagic Fever ◽  
Human Cells ◽  
Transient Expression Assay ◽  
Virus Like Particles ◽  
Modified Vaccinia Virus Ankara

ABSTRACT There are currently no approved therapeutics or vaccines to treat or protect against the severe hemorrhagic fever and death caused by Ebola virus (EBOV). Ebola virus-like particles (EBOV VLPs) consisting of the matrix protein VP40, the glycoprotein (GP), and the nucleoprotein (NP) are highly immunogenic and protective in nonhuman primates against Ebola virus disease (EVD). We have constructed a modified vaccinia virus Ankara-Bavarian Nordic (MVA-BN) recombinant coexpressing VP40 and GP of EBOV Mayinga and the NP of Taï Forest virus (TAFV) (MVA-BN-EBOV-VLP) to launch noninfectious EBOV VLPs as a second vaccine modality in the MVA-BN-EBOV-VLP-vaccinated organism. Human cells infected with either MVA-BN-EBOV-VLP or MVA-BN-EBOV-GP showed comparable GP expression levels and transport of complex N-glycosylated GP to the cell surface. Human cells infected with MVA-BN-EBOV-VLP produced large amounts of EBOV VLPs that were decorated with GP spikes but excluded the poxviral membrane protein B5, thus resembling authentic EBOV particles. The heterologous TAFV NP enhanced EBOV VP40-driven VLP formation with efficiency similar to that of the homologous EBOV NP in a transient-expression assay, and both NPs were incorporated into EBOV VLPs. EBOV GP-specific CD8 T cell responses were comparable between MVA-BN-EBOV-VLP- and MVA-BN-EBOV-GP-immunized mice. The levels of EBOV GP-specific neutralizing and binding antibodies, as well as GP-specific IgG1/IgG2a ratios induced by the two constructs, in mice were also similar, raising the question whether the quality rather than the quantity of the GP-specific antibody response might be altered by an EBOV VLP-generating MVA recombinant. IMPORTANCE The recent outbreak of Ebola virus (EBOV), claiming more than 11,000 lives, has underscored the need to advance the development of safe and effective filovirus vaccines. Virus-like particles (VLPs), as well as recombinant viral vectors, have proved to be promising vaccine candidates. Modified vaccinia virus Ankara-Bavarian Nordic (MVA-BN) is a safe and immunogenic vaccine vector with a large capacity to accommodate multiple foreign genes. In this study, we combined the advantages of VLPs and the MVA platform by generating a recombinant MVA-BN-EBOV-VLP that would produce noninfectious EBOV VLPs in the vaccinated individual. Our results show that human cells infected with MVA-BN-EBOV-VLP indeed formed and released EBOV VLPs, thus producing a highly authentic immunogen. MVA-BN-EBOV-VLP efficiently induced EBOV-specific humoral and cellular immune responses in vaccinated mice. These results are the basis for future advancements, e.g., by including antigens from various filoviral species to develop multivalent VLP-producing MVA-based filovirus vaccines.

scholarly journals Recombinant Modified Vaccinia Virus Ankara (MVA) Vaccines Efficiently Protect Cockatiels Against Parrot Bornavirus Infection and Proventricular Dilatation Disease

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1130 ◽  
Author(s):  
Isabell Rall ◽  
Ralf Amann ◽  
Sara Malberg ◽  
Christiane Herden ◽  
Dennis Rubbenstroth
Keyword(s):  
Vaccinia Virus ◽  
Challenge Infection ◽  
Control Group ◽  
Viral Loads ◽  
Breeding Populations ◽  
Modified Vaccinia Virus Ankara ◽  
Associated Lesions ◽  
Unvaccinated Control ◽  
Causative Agents ◽  
Proventricular Dilatation Disease

Parrot bornaviruses (PaBVs) are the causative agents of proventricular dilatation disease (PDD), a chronic and often fatal neurologic disorder in Psittaciformes. The disease is widely distributed in private parrot collections and threatens breeding populations of endangered species. Thus, immunoprophylaxis strategies are urgently needed. In previous studies we demonstrated a prime-boost vaccination regime using modified vaccinia virus Ankara (MVA) and Newcastle disease virus (NDV) constructs expressing the nucleoprotein and phosphoprotein of PaBV-4 (MVA/PaBV-4 and NDV/PaBV-4, respectively) to protect cockatiels (Nymphicus hollandicus) against experimental challenge infection. Here we investigated the protective effect provided by repeated immunization with either MVA/PaBV-4, NDV/PaBV-4 or Orf virus constructs (ORFV/PaBV-4) individually. While MVA/PaBV-4-vaccinated cockatiels were completely protected against subsequent PaBV-2 challenge infection and PDD-associated lesions, the course of the challenge infection in NDV/PaBV-4- or ORFV/PaBV-4-vaccinated birds did not differ from the unvaccinated control group. We further investigated the effect of vaccination on persistently PaBV-4-infected cockatiels. Remarkably, subsequent immunization with MVA/PaBV-4 and NDV/PaBV-4 neither induced obvious immunopathogenesis exacerbating the disease nor reduced viral loads in the infected birds. In summary, we demonstrated that vaccination with MVA/PaBV-4 alone is sufficient to efficiently prevent PaBV-2 challenge infection in cockatiels, providing a suitable vaccine candidate against avian bornavirus infection and bornavirus-induced PDD.

scholarly journals Transient Host Range Selection for Genetic Engineering of Modified Vaccinia Virus Ankara

BioTechniques ◽  
2000 ◽  
Vol 28 (6) ◽  
pp. 1137-1148 ◽  
Author(s):  
C. Staib ◽  
I. Drexler ◽  
M. Ohlmann ◽  
S. Wintersperger ◽  
V. Erfle ◽  
...  
Keyword(s):  
Genetic Engineering ◽  
Vaccinia Virus ◽  
Host Range ◽  
Modified Vaccinia Virus Ankara ◽  
Selection For ◽  
Range Selection

scholarly journals Immediate-Early Expression of a Recombinant Antigen by Modified Vaccinia Virus Ankara Breaks the Immunodominance of Strong Vector-Specific B8R Antigen in Acute and Memory CD8 T-Cell Responses

2010 ◽  
Vol 84 (17) ◽  
pp. 8743-8752 ◽  
Author(s):  
Karen Baur ◽  
Kay Brinkmann ◽  
Marc Schweneker ◽  
Juliane Pätzold ◽  
Christine Meisinger-Henschel ◽  
...  
Keyword(s):  
T Cell ◽  
Vaccinia Virus ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Immediate Early ◽  
Egfp Expression ◽  
Cell Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Memory Cd8 T Cell ◽  
Early Late

ABSTRACT Efficient T-cell responses against recombinant antigens expressed by vaccinia virus vectors require expression of these antigens in the early phase of the virus replication cycle. The kinetics of recombinant gene expression in poxviruses are largely determined by the promoter chosen. We used the highly attenuated modified vaccinia virus Ankara (MVA) to determine the role of promoters in the induction of CD8 T-cell responses. We constructed MVA recombinants expressing either enhanced green fluorescent protein (EGFP) or chicken ovalbumin (OVA), each under the control of a hybrid early-late promoter (pHyb) containing five copies of a strong early element or the well-known early-late p7.5 or pS promoter for comparison. In primary or cultured cells, EGFP expression under the control of pHyb was detected within 30 min, as an immediate-early protein, and remained higher over the first 6 h of infection than p7.5- or pS-driven EGFP expression. Repeated immunizations of mice with recombinant MVA expressing OVA under the control of the pHyb promoter led to superior acute and memory CD8 T-cell responses compared to those to p7.5- and pS-driven OVA. Moreover, OVA expressed under the control of pHyb replaced the MVA-derived B8R protein as the immunodominant CD8 T-cell antigen after three or more immunizations. This is the first demonstration of an immediate-early neoantigen expressed by a poxviral vector resulting in superior induction of neoantigen-specific CD8 T-cell responses.

scholarly journals A Single Immunization With Modified Vaccinia Virus Ankara-Based Influenza Virus H7 Vaccine Affords Protection in the Influenza A(H7N9) Pneumonia Ferret Model

2014 ◽  
Vol 211 (5) ◽  
pp. 791-800 ◽  
Author(s):  
J. H. C. M. Kreijtz ◽  
L. C. M. Wiersma ◽  
H. L. M. De Gruyter ◽  
S. E. Vogelzang-van Trierum ◽  
G. van Amerongen ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Vaccinia Virus ◽  
Influenza A ◽  
Modified Vaccinia Virus Ankara

scholarly journals Novel Recombinant Mycobacterium bovis BCG, Ovine Atadenovirus, and Modified Vaccinia Virus Ankara Vaccines Combine To Induce Robust Human Immunodeficiency Virus-Specific CD4 and CD8 T-Cell Responses in Rhesus Macaques

2010 ◽  
Vol 84 (12) ◽  
pp. 5898-5908 ◽  
Author(s):  
Maximillian Rosario ◽  
Richard Hopkins ◽  
John Fulkerson ◽  
Nicola Borthwick ◽  
Máire F. Quigley ◽  
...  
Keyword(s):  
T Cell ◽  
Vaccinia Virus ◽  
Mycobacterium Bovis ◽  
Ex Vivo ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Hiv 1

ABSTRACT Mycobacterium bovis bacillus Calmette-Guérin (BCG), which elicits a degree of protective immunity against tuberculosis, is the most widely used vaccine in the world. Due to its persistence and immunogenicity, BCG has been proposed as a vector for vaccines against other infections, including HIV-1. BCG has a very good safety record, although it can cause disseminated disease in immunocompromised individuals. Here, we constructed a recombinant BCG vector expressing HIV-1 clade A-derived immunogen HIVA using the recently described safer and more immunogenic BCG strain AERAS-401 as the parental mycobacterium. Using routine ex vivo T-cell assays, BCG.HIVA401 as a stand-alone vaccine induced undetectable and weak CD8 T-cell responses in BALB/c mice and rhesus macaques, respectively. However, when BCG.HIVA401 was used as a priming component in heterologous vaccination regimens together with recombinant modified vaccinia virus Ankara-vectored MVA.HIVA and ovine atadenovirus-vectored OAdV.HIVA vaccines, robust HIV-1-specific T-cell responses were elicited. These high-frequency T-cell responses were broadly directed and capable of proliferation in response to recall antigen. Furthermore, multiple antigen-specific T-cell clonotypes were efficiently recruited into the memory pool. These desirable features are thought to be associated with good control of HIV-1 infection. In addition, strong and persistent T-cell responses specific for the BCG-derived purified protein derivative (PPD) antigen were induced. This work is the first demonstration of immunogenicity for two novel vaccine vectors and the corresponding candidate HIV-1 vaccines BCG.HIVA401 and OAdV.HIVA in nonhuman primates. These results strongly support their further exploration.

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