Modified vaccinia virus Ankara as antigen delivery system: how can we best use its potential?

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.

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

BioTechniques ◽

10.2144/00286st04 ◽

2000 ◽

Vol 28 (6) ◽

pp. 1137-1148 ◽

Cited By ~ 58

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

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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

Journal of Virology ◽

10.1128/jvi.00604-10 ◽

2010 ◽

Vol 84 (17) ◽

pp. 8743-8752 ◽

Cited By ~ 33

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.

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Vaccine potential of plasma bead-based dual antigen delivery system against experimental murine candidiasis

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2015.07.047 ◽

2015 ◽

Vol 81 ◽

pp. 100-111 ◽

Cited By ~ 4

Author(s):

Ejaj Ahmad ◽

Qamar Zia ◽

Munazza Tamkeen Fatima ◽

Mohammad Owais ◽

Mohammed Saleemuddin

Keyword(s):

Delivery System ◽

Antigen Delivery ◽

Vaccine Potential

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

The Journal of Infectious Diseases ◽

10.1093/infdis/jiu528 ◽

2014 ◽

Vol 211 (5) ◽

pp. 791-800 ◽

Cited By ~ 23

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

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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

Journal of Virology ◽

10.1128/jvi.02607-09 ◽

2010 ◽

Vol 84 (12) ◽

pp. 5898-5908 ◽

Cited By ~ 19

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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Removal of the C6 Vaccinia Virus Interferon-β Inhibitor in the Hepatitis C Vaccine Candidate MVA-HCV Elicited in Mice High Immunogenicity in Spite of Reduced Host Gene Expression

Viruses ◽

10.3390/v10080414 ◽

2018 ◽

Vol 10 (8) ◽

pp. 414 ◽

Cited By ~ 7

Author(s):

María Q. Marín ◽

Patricia Pérez ◽

Carmen E. Gómez ◽

Carlos Óscar S. Sorzano ◽

Mariano Esteban ◽

...

Keyword(s):

Gene Expression ◽

Hepatitis C ◽

T Cell ◽

Vaccinia Virus ◽

Vaccine Candidate ◽

Human Monocyte ◽

Cd8 T Cell ◽

Inhibitory Effect ◽

Effector Memory ◽

Modified Vaccinia Virus Ankara

Hepatitis C virus (HCV) represents a major global health problem for which a vaccine is not available. Modified vaccinia virus Ankara (MVA)-HCV is a unique HCV vaccine candidate based in the modified vaccinia virus Ankara (MVA) vector expressing the nearly full-length genome of HCV genotype 1a that elicits CD8+ T-cell responses in mice. With the aim to improve the immune response of MVA-HCV and because of the importance of interferon (IFN) in HCV infection, we deleted in MVA-HCV the vaccinia virus (VACV) C6L gene, encoding an inhibitor of IFN-β that prevents activation of the interferon regulatory factors 3 and 7 (IRF3 and IRF7). The resulting vaccine candidate (MVA-HCV ΔC6L) expresses all HCV antigens and deletion of C6L had no effect on viral growth in permissive chicken cells. In human monocyte-derived dendritic cells, infection with MVA-HCV ΔC6L triggered severe down-regulation of IFN-β, IFN-β-induced genes, and cytokines in a manner similar to MVA-HCV, as defined by real-time polymerase chain reaction (PCR) and microarray analysis. In infected mice, both vectors had a similar profile of recruited immune cells and induced comparable levels of adaptive and memory HCV-specific CD8+ T-cells, mainly against p7 + NS2 and NS3 HCV proteins, with a T cell effector memory (TEM) phenotype. Furthermore, antibodies against E2 were also induced. Overall, our findings showed that while these vectors had a profound inhibitory effect on gene expression of the host, they strongly elicited CD8+ T cell and humoral responses against HCV antigens and to the virus vector. These observations add support to the consideration of these vectors as potential vaccine candidates against HCV.

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