Studies on poxvirus infections in irradiated animals

Werner, G. T.; Jentzsch, U.; Metzger, Emy; Simon, J.

doi:10.1007/bf01322704

Cited by 44 publications

(28 citation statements)

References 12 publications

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“…gan in the late 1950s after attenuation of the parent strain CVA in chicken embryo fibroblasts. Since that time, MVA has been evaluated in several animal models as well as in humans (22,30,43). During the 1970s, more than 120,000 people were immunized with MVA (37).…”

Section: Discussionmentioning

confidence: 99%

“…During the 1970s, more than 120,000 people were immunized with MVA (37). Reports reflect a good safety profile for MVA, including safe administration to immunocompromised animals (38,43). However, the specific determinants of MVA-induced immunity compared with those induced by replication-competent vaccinia virus have only recently been studied (5,45).…”

Section: Discussionmentioning

confidence: 99%

“…Earlier work with MVA demonstrated its safety and its ability to protect against the development of poxvirus infections in several animal models (22,30,43). Recently, MVA immunization has been shown to provide protection against a pulmonary vaccinia virus challenge (4,11).…”

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confidence: 99%

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Modified Vaccinia Virus Ankara Immunization Protects against Lethal Challenge with Recombinant Vaccinia Virus Expressing Murine Interleukin-4

McCurdy

Rutigliano

Johnson

et al. 2004

J Virol

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Recent events have raised concern over the use of pathogens, including variola virus, as biological weapons. Vaccination with Dryvax is associated with serious side effects and is contraindicated for many people, and the development of a safer effective smallpox vaccine is necessary. We evaluated an attenuated vaccinia virus, modified vaccinia virus Ankara ؉ -or CD8 ؉ -T-cell depletion reduced the protection against a high-dose vSC8-mIL4 challenge, and the depletion of both T-cell subsets was associated with severe illness and higher vaccinia virus titers. Thus, MVA induces broad humoral and cellular immune responses that can independently protect against a molecularly modified lethal poxvirus challenge in mice. These data support the continued development of MVA as an alternative candidate vaccine for smallpox.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Modified Vaccinia Virus Ankara Immunization Protects against Lethal Challenge with Recombinant Vaccinia Virus Expressing Murine Interleukin-4

McCurdy

Rutigliano

Johnson

et al. 2004

J Virol

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Section: Introductionmentioning

confidence: 99%

“…It affects the pattern of host cell gene expression [29] and generates an environment favourable for induction of CD8 + T cells [30]. After vaccination, recombinant MVA (rMVA) delivers a pulse of the pathogen-derived antigens and is cleared from the body of normal and immunocompromised animals within days to weeks after delivery [31][32][33][34][35].Here, we investigated the effect of a gross diminution of CD4 + T cell help on the functional development of CD8 + T cells from their antigenically naive precursors following administration of an MVA-vectored vaccine. To overcome the low frequency of naive cells, we utilised mouse strain F5 transgenic for TCR recognizing epitope ASNENMDAM and vaccine MVA.HIVA-NP [36], a derivative of the current clinical trial vaccine MVA.HIVA [37].…”

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confidence: 99%

Altered primary CD8⁺ T cell response to a modified virus Ankara(MVA)‐vectored vaccine in the absence of CD4⁺ T cell help

Estcourt¹,

McMichael²,

Hanke³

2005

Eur J Immunol

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T cell receptor-transgenic F5 mice were used to assess primary CD8 + T cell responses to a modified virus Ankara (MVA)-vectored vaccine in the absence of CD4 + T cell help. Naive, CD8-enriched, CFSE-labelled F5 cells were transferred into normal or CD4 + celldepleted mice and the mice were vaccinated with MVA.HIVA-NP. At different time points during the primary response, F5 cells were re-isolated and analysed on divisional basis for a number of parameters. We demonstrated that the primary CD8 + T cell response in the absence of CD4 + T cell help differed from that in normal CD4 + cellundepleted mice. While in the absence of CD4 + T cell help, the initial migratory progress from the local response to a systemic one was not grossly affected, the proportion of dying F5 cells during the expansion phase was markedly increased and resulted in an overall smaller expansion and significantly decreased frequency of CD8 + T cell memory after contraction. T cells primed without help displayed accelerated proliferation and activation, while expression of interferon-c remained similar. These phenomena were observed in the lymph nodes draining the MVA.HIVA-NP immunization site and were similar, but delayed by 2-3 days in spleen and non-draining lymph nodes. IntroductionCD8 + T cells form an important part of the immune defence against many intracellular pathogens including viruses. Historically, CD8 + T cell responses against viral infections were considered to be independent from 'help' provided by CD4 + T cells. This was explained by direct activation of antigen-presenting DC by viruses, which provided ligands for Toll-like receptors and proinflammatory signals [1][2][3]. Recently, this view was revised by studies of non-inflammatory antigens which suggested that while primary CD8 + T cell response was CD4 + T cell-independent, secondary CD8 + T cell response, i.e. development of functional memory, was dependent on CD4 + T cell help during priming. These data led to the formulation of a programming model [4][5][6]. In contrast, another set of recent studies pointed towards an environmental model and proposed that CD4 + T cells were required to enhance survival of fully functional memory CD8 + T cells rather than imparting essential programming during the primary response [7,8]. The differences in these conclusions may be explained by the use of different antigens and immunization protocols, which might lead to differential activation of DC. Collectively, these and other experiments [9][10][11][12][13] not required for triggering the CD8 + T cell program of multiple cell divisions, effector function maturation and cell number contraction, but was needed for differentiation into functional CD8 + T cell memory and/or its maintenance.To date, most studies investigated secondary responses to make conclusions about the dependence of the CD8 + T cell responses on CD4 help. This is partially because induction of a good memory is the ultimate aim of a successful vaccination, but also because primary CD8 + T cell responses to non-inf...

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Vaccine route, dose and type of delivery vector determine patterns of primary CD8⁺ T cell responses

et al. 2005

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The dynamics of primary CD8 + T cell responses following administration of modified virus Ankara (MVA)-and DNA-vectored vaccines was investigated in a mouse model. To overcome the low frequency of naive antigen-specific precursors and follow the early expansion events, naive CFSE-labelled T cell receptor-transgenic F5 lymphocytes were transferred into syngeneic non-transgenic recipients prior to vaccination. Using the i.d., i.v. and i.m. routes and increasing recombinant MVA (rMVA) vaccine doses, the primary response was analysed on a divisional basis at local and distant lymphoid organs at various times after vaccination. The results indicated that F5 cell divisions were initiated in the local draining lymph nodes and cells only after five to six divisions appeared at more distant sites. The rMVA dose affected frequencies of cells entering division and at the peak response. When priming induced by rMVA and plasmid DNA was compared, dramatic differences in the cycling patterns were observed with plasmid DNA inducing a response slower and more sustained over the first 2 wk than rMVA. Both rMVA and DNA induced comparable IFN-c production, which increased with cell divisions. Taken together, the vaccine type, dose and route have a strong influence on the spatial and temporal patterns of initial T cell responses. IntroductionInduction of cell-mediated immunity is the goal of many current vaccine strategies. This is particularly true for pathogens such as HIV-1, against which induction of broadly neutralizing antibodies has proven extremely difficult [1]. A few vaccine candidates capable of stimulating high levels of HIV-1-specific CD8 + T cells in mice and non-human primates have entered clinical trials in humans. Although more complete results from many of these human trials are still awaited, emerging data indicate that the overall immunogenicities compared to animal models are lower. Thus, the search for novel strategies maximizing T cell induction remains the focus of AIDS vaccine development for the foreseeable future. This will be greatly facilitated by a better understanding of the processes that underlie induction of cellular immunity and the special features that individual vaccine vectors have to offer. Currently, among the most vigorously pursued approaches inducing T cell immunity are vaccines vectored by naked DNA, attenuated poxviruses and adenoviruses and their heterologous prime-boost combinations. We have been testing in clinical trials a protocol consisting of DNA priming and boosting with modified virus Ankara (MVA) [2,3]. Plasmid DNA as a vaccine vector has a number of attractive features, although the immunogenicity of DNA-vectored vaccines alone has been unimpressive [3][4][5][6][7] possibly due to the lower vaccine doses used in humans compared to those applied to experimental animals (e.g. per body surface area). MVA is a disabled poxvirus with an excellent safety and immunogenicity record [3,[8][9][10]. Extensive clinical studies of recombinant MVA for HIV-1 [3,10], Plasmodium falciparum ma...

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Studies on poxvirus infections in irradiated animals

Cited by 44 publications

References 12 publications

Modified Vaccinia Virus Ankara Immunization Protects against Lethal Challenge with Recombinant Vaccinia Virus Expressing Murine Interleukin-4

Modified Vaccinia Virus Ankara Immunization Protects against Lethal Challenge with Recombinant Vaccinia Virus Expressing Murine Interleukin-4

Altered primary CD8⁺ T cell response to a modified virus Ankara(MVA)‐vectored vaccine in the absence of CD4⁺ T cell help

Vaccine route, dose and type of delivery vector determine patterns of primary CD8⁺ T cell responses

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Studies on poxvirus infections in irradiated animals

Cited by 44 publications

References 12 publications

Modified Vaccinia Virus Ankara Immunization Protects against Lethal Challenge with Recombinant Vaccinia Virus Expressing Murine Interleukin-4

Modified Vaccinia Virus Ankara Immunization Protects against Lethal Challenge with Recombinant Vaccinia Virus Expressing Murine Interleukin-4

Altered primary CD8+ T cell response to a modified virus Ankara(MVA)‐vectored vaccine in the absence of CD4+ T cell help

Vaccine route, dose and type of delivery vector determine patterns of primary CD8+ T cell responses

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Altered primary CD8⁺ T cell response to a modified virus Ankara(MVA)‐vectored vaccine in the absence of CD4⁺ T cell help

Vaccine route, dose and type of delivery vector determine patterns of primary CD8⁺ T cell responses