Market implementation of the MVA platform for pre-pandemic and pandemic influenza vaccines: A quantitative key opinion leader analysis

Ramezanpour, Bahar; Pronker, Esther; Kreijtz, Joost H. C. M.; Osterhaus, Albert D. M. E.; Claassen, Eric

doi:10.1016/j.vaccine.2015.04.086

Cited by 11 publications

(16 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Especially promising vectors are highly attenuated poxviruses, including modified vaccinia virus Ankara (MVA) [1]. MVA has been attenuated by repeated passaging in chicken fibroblast cultures [2], and its properties as potential human vector vaccine have been well characterized [1,[3][4][5][6][7][8][9][10][11]. Various MVA recombinants that express different viral heterologous antigens have been generated and extensively tested in pre-clinical and clinical trials as candidate vaccine against diseases such as AIDS, influenza, severe acute respiratory syndrome (SARS) and human respiratory syncytial virus (RSV) infection [7,[9][10][11].…”

Section: Introductionmentioning

confidence: 99%

High-cell-density cultivations to increase MVA virus production

Vázquez-Ramírez

Genzel

Jordan³

et al. 2018

Vaccine

View full text Add to dashboard Cite

Increasing the yield and the productivity in cell culture-based vaccine manufacturing using high-cell-density (HCD) cultivations faces a number of challenges. For example, medium consumption should be low to obtain a very high concentration of viable host cells in an economical way but must be balanced against the requirement that accumulation of toxic metabolites and limitation of nutrients have to be avoided. HCD cultivations should also be optimized to avoid unwanted induction of apoptosis or autophagy during the early phase of virus infection. To realize the full potential of HCD cultivations, a rational analysis of the cultivation conditions of the appropriate host cell line together with the optimal infection conditions for the chosen viral vaccine strain needs to be performed for each particular manufacturing process. We here illustrate our strategy for production of the modified vaccinia Ankara (MVA) virus isolate MVA-CR19 in the avian suspension cell line AGE1.CR.pIX at HCD. As a first step we demonstrate that the adjustment of the perfusion rate strictly based on the measured cell concentration and the glucose consumption rate of cells enables optimal growth in a 0.8 L bioreactor equipped with an ATF2 system. Concentrations up to 57 × 10 cells/mL (before infection) were obtained with a viability exceeding 95%, and a maximum specific cell growth rate of 0.019 h (doubling time = 36.5 h). However, not only the cell-specific MVA-CR19 virus yield but also the volumetric productivity was reduced compared to infections at conventional-cell-density (CCD). To facilitate optimization of the virus propagation phase at HCD, a larger set of feeding strategies was analyzed in small-scale cultivations using shake flasks. Densities up to 63 × 10 cells/mL were obtained at the end of the cell growth phase applying a discontinuous perfusion mode (semi-perfusion) with the same cell-specific perfusion rate as in the bioreactor (0.060 nL/(cell d)). At this cell concentration, a medium exchange at time of infection was required to obtain expected virus yields during the first 24 h after infection. Applying an additional fed-batch feeding strategy during the whole virus replication phase resulted in a faster virus titer increase during the first 36 h after infection. In contrast, a semi-continuous virus harvest scheme improved virus accumulation and recovery at a rather later stage of infection. Overall, a combination of both fed-batch and medium exchange strategies resulted in similar cell-specific virus yields as those obtained for CCD processes but 10-fold higher MVA-CR19 titers, and four times higher volumetric productivity.

show abstract

Section: Introductionmentioning

confidence: 99%

High-cell-density cultivations to increase MVA virus production

Vázquez-Ramírez

Genzel

Jordan³

et al. 2018

Vaccine

View full text Add to dashboard Cite

show abstract

“…The virology has been investigated and such analysis has been already presented on the viral biology [112]. The market implementation of the vaccine for the influenza pandemic to highlight the burden due to the influenza has also been analyzed in similar way [113]. The realization of the HIV vaccine, like anyone of those listed in the governmental schedules for vaccination is due for the last three decades of reserach.…”

Section: Methods Swot Analysismentioning

confidence: 99%

Conventional Vaccine to Prevent AIDS A Paradigm or A Paradox? A SWOT Analysis

Christdas¹

2016

HIV Curr Res

View full text Add to dashboard Cite

AIDS as a disease afflicts mankind for more than 3 decades. HIV, the causative is not yet checked with a prophylactic vaccine. The plausibility of the prevention by conventional prophylactic strategies based on Jenner's conventional method of inducing memory response is reviewed here. In order to find the right direction towards achieving this goal, a SWOT analysis is represented here with a Venn diagram. Our increasing awareness on the viral genome and the antiviral treatment with the sensitive diagnostic tools strengthen the efforts, while the viral nature privileges its replenishment by hampering the host immune memory. Though antiviral drugs promise a notable degree of control, they render selection pressure favoring viral escapism with perking quasispecies or circulating recombinant forms (CRF). Few historical clinical trials teach us to frame new opportunities for the conduct of such trials that assures safety. The knowledge has exponentially increased on the host immune response, human genetics, retrovirology, drug development, gene delivery system to understand that HIV is the only pathogen that had the greatest consumption of our time and resources. The technological advancements add to our strength. However, the virus with its biological features proves its intrinsic competency for survival. Though the antiviral therapy confers some hope, the resistant forms pose a threat to their continuation. It emphasizes the need for prevention and suggests novel, unconventional prophylaxis. Treatment as a means of prevention and the use of immunomodulators to decrease the disease progression can help us to win the belligerence against AIDS.

show abstract

“…The present paper only deals with vectors that are actually used as vaccines and not just for the production of immunogens. Our previous study provides additional insights regarding the strengths, weaknesses, opportunities, and threats of such technology [12]. Vectors can either be fully replicative or only cause abortive infection, still allowing the expression of the desired immunogens.…”

Section: Introductionmentioning

confidence: 99%

Vector-based genetically modified vaccines: Exploiting Jenner’s legacy

Ramezanpour

Haan

Osterhaus

et al. 2016

Vaccine

Self Cite

View full text Add to dashboard Cite

The global vaccine market is diverse while facing a plethora of novel developments. Genetic modification (GM) techniques facilitate the design of 'smarter' vaccines. For many of the major infectious diseases of humans, like AIDS and malaria, but also for most human neoplastic disorders, still no vaccines are available. It may be speculated that novel GM technologies will significantly contribute to their development. While a promising number of studies is conducted on GM vaccines and GM vaccine technologies, the contribution of GM technology to newly introduced vaccines on the market is disappointingly limited. In this study, the field of vector-based GM vaccines is explored. Data on currently available, actually applied, and newly developed vectors is retrieved from various sources, synthesised and analysed, in order to provide an overview on the use of vector-based technology in the field of GM vaccine development. While still there are only two vector-based vaccines on the human vaccine market, there is ample activity in the fields of patenting, preclinical research, and different stages of clinical research. Results of this study revealed that vector-based vaccines comprise a significant part of all GM vaccines in the pipeline. This study further highlights that poxviruses and adenoviruses are among the most prominent vectors in GM vaccine development. After the approval of the first vectored human vaccine, based on a flavivirus vector, vaccine vector technology, especially based on poxviruses and adenoviruses, holds great promise for future vaccine development. It may lead to cheaper methods for the production of safe vaccines against diseases for which no or less perfect vaccines exist today, thus catering for an unmet medical need. After the introduction of Jenner's vaccinia virus as the first vaccine more than two centuries ago, which eventually led to the recent eradication of smallpox, this and other viruses may now be the basis for constructing vectors that may help us control other major scourges of mankind.

show abstract

Market implementation of the MVA platform for pre-pandemic and pandemic influenza vaccines: A quantitative key opinion leader analysis

Cited by 11 publications

References 51 publications

High-cell-density cultivations to increase MVA virus production

High-cell-density cultivations to increase MVA virus production

Conventional Vaccine to Prevent AIDS A Paradigm or A Paradox? A SWOT Analysis

Vector-based genetically modified vaccines: Exploiting Jenner’s legacy

Contact Info

Product

Resources

About