One Health Vaccines

Overview

Vaccination against disease is an integral part of prevention of communicable disease worldwide. Besides reducing incidence of a disease wheter it be in animals or humans, it also reduces social and economic burden worlwide.

The key consideration in preventing communicable disease and specifically dealing with a pandemic or epidemic outbreak of disease is timely production and deployment of vaccines.

The needs of vaccine manufacturing processes are to offer a broad portfolio as well as faster reaction times to deal with pandemics and epidemics.

Esco Aster is committed to providing vaccines that are accessible and affordable to the Asian and global population. It does so through its proprietary Tide Motion® platform that can rapidly speed up the manufacturing process of Viral vaccines.

Among the numerous factors to be taken into consideration are cultivation systems and scale-up strategies. In this regard, the Tide Motion® Bioreactors offer:
  • Novel platforms designed to achieve high cell densities
  • Highly scalable production process
  • Excellent options to replace conventional culture systems in terms of economy, ease of production, higher process control, and high viral titers while ensuring product quality.
  • Significantly lower cost of goods as a consequence of high viral titers

Capabilities

Master and working cell banks for virus culture

Proprietary animal-component free culture media suitable for cultivation of certain cell subtrates

Optimisation and process development for cultivatio of cell subtrates for virus production

Process optimization and manufacturing of animal and human viral vaccines

Downstream processing for viral vaccines including concentration, purification and analytical services

Characterization and analysis of purified viral vaccines for endotoxins, host cell DNA and protein contamination and final viral titer

Sterility testing, fill and finish services

Cell banking and virus banking services

Esco Aster's Vaccine Production:
An Overview

The Tide Motion® manufacturing platform offers a smooth and seamless vaccine production workflow.

In addition, a modularly integrated system with our Cell Processing Isolator (CPI), helps to localize vaccine prodction making it more affordable - in terms of CAPEX & OPEX - for developing countries by ensuring a smooth bioprocessing workflow.

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Esco Aster's Portfolio of Veterinary
and Human Vaccines

With an aim of ensuring a reliability of vaccine supply and immunization to support the growing livestock and poultry industry. Tide Motion® Bioreactors are indeed the means of achieveing high-cell density working cell bank cultures (HD WCB) to support scalable production of veterinary vaccines.

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Adherent cell lines commonly used in veterinary vaccine production and constitues our Animal Vaccine Portfolio:

  • Vero for PPR viruses, PEDV and Rift Valley Virus
  • BHK-21 for Animal Rabies
  • MARC-145 for PRRSV
  • ST for Swine vaccines such as Hog Cholera, and PEDV
  • CEF primary lines for Marek's Virus
  • Lamb testis cell lines for LSD Virus
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Human Vaccines

The importance of human vaccines cannot be over-emphasized in terms of its impact on human health and lives. Timely vaccine production and deployment and its impact on human lives is crucial. Transmission of diseases from animals to humans and reassortment of viruses poses a significant threat globally and annual vaccination is an important strategy to prevent infection during pandemic outbreaks.

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Adherent cell lines commonly used in human vaccine production and constitues our Human Vaccine portfolio:

  • Vero - Influenza, Japanese Encephalitis Virus, Yellow Fever
  • MDCK - Influenza
  • BHK-21 - Hand,Foot and Mouth Disease
  • MRC-5 - Human Rabies, Rubella
  • HuH 7.5 - Hepatitis C
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High Viral Titers with TideXcell™ Bioreactors

Culture conditions tend to be variable for different cell lines and very high cell densities; hence vaccines with a high titer which are capable of eliciting good immune responses have been achieved in TideXcell™ bioreactors.

As a consequence of high cell densities and high viral titers in the range of 8 log10 frequently the Tide Motion® bioreactors are able to effectively replace static culture systems as shown below:

Swine Vaccine

Vaccine 2D Culture system
(No. of units)
Tide Motion® Bioreactor
(No. of units)
Hog cholera Roller bottles
(2500cm2) > 123
TideXcell™ - 002 (1)
PEDV T150-flasks > 285 CelCradle™ - 500A (1)
PRRSV T175 - flasks > 132 CelCrade™ - 500A (1)

H5N1 and H1N1

Vaccine Roller Bottle
(850 cm2, 2L)
TideXcell™
(10L)
H5N1 1000-2000 1
H1N1 1000 1

Rabbies Vaccine

CelCradle™ - 500A Roller Bottles Roux Bottles
Media 1000 ml 4550 ml 4550 ml
Fetal Calf Serum 100 ml 455 ml 455 ml
Culture System 1 26 13
Filtration - Y Y
Washing - Y Y
Packaging - Y Y
Sterilization - Y Y
Virus Titre 106-7LD50/ml 106LD50/ml 106LD50/ml

Peste des Petits Ruminants

Equivalence
Titer of virus obtained from vs CelCradle™
32 roller bottles = 1 CelCradle-500 A
(Volume = 8L)
Titer = 7 X TCID50 per ml
(Volume = 2.5L dilutted to 8L)
Titer = 7.167 TCID50 per ml

Our deltaFLU Production

The vaccines against deltaFLU have been process optimized and scaled up at Esco Aster. The deltaFLU technology which is proprietary to one of Aster’s collaborators is an attenuated recombinant influenza virus that lacks the IFN –Y antagonist and thus has a natural self-adjuvanting action.

A Vero-cell based production process has yielded titers of >8.0log 10. An efficient scale-up, downstream processing and analysis of the final product ensures a smooth and seamless work flow as outlined below:

Fish Vaccines

Within the sphere on One Health, the issue of antimicrobial resistance is interlinked with the misuse and overuse of antimicrobial products for health management of fish farms. These drugs are freely in contact with water systems and in some cases, remain as chemical residues considered as food hazard. Vaccination helps to prevent the release of these compounds to ensure healthy ecosystem. We help collaborators in providing autogenous vaccines tailored for specific disease and farm.


Type of Fish Vaccine Description Advantages Disadvantages Commercialized Vaccine Examples
Conventional Inactivated/Killed Physically or chemically manipulated microbe which loses its ability to infect/replicate
  • Less expensive to produce compared to other types
  • Stable under different conditions
  • Requires use of adjuvants as induced immunity is weaker/short-lived
  • Toxic/systemic reactions to adjuvants
  • Less immunogenic
Inactivated Infectious Salmon Anemia Virus (ISAV)
Attenuated live vaccine Modified virus/bacteria with low virulence for the fish species
  • More immunogenic compared to killed vaccine
  • Long lasting immunity
  • Risks associated with virulence
  • Contamination with other live microorganisms
Attenuated Arthrobacter vaccine against bacterial kidney disease (BKD)
Alternative Vaccine Technologies Subunit Use of antigenic/immunogenic parts
  • Highly characterized
  • Allows easier transport (can be freeze-dried)
  • Requires adjuvants as associated with low immunogenicity
  • May require multiple immunizations (higher labor requirements)
G glycoprotein for Spring viremia of carp virus
VLPs Mofidied subunit vaccine comprise of viral capsid and target proteins
  • High immunogenicity
  • No reversion to virulence compared to live vaccine
  • Allows chimeric VLPs
  • May be unstable during downstream processing
  • Variable expression in different host systems
Nervous necrosis virus (NNV) VLP vaccines
DNA Plasmid which carries gene coding for antigenic protein
  • Activate strong immunity
  • Rapid development
  • Considered safer than whole organism
  • Needs protection for entry
  • Risk of insertion into the genome
DNA vaccine against IHNV
DNA vaccine against IHNV Can be non-amplifying or self-amplifying
  • No risk for infection or insertion
  • Stimulates strong immunity
  • In-vitro transcription may be expensive
  • Optimal delivery is challenging
Vaccine candidate only: Salmonid alphavirus 3 (SAV3)-based replicaon against ISAV

Capabilities for Autogenous Vaccines

Cell and virus banking for specific pathogenic strains
Process optimization and production of autogenous vaccines
QC testing for batch release (in-vitro tests)

Reference:
  1. Ma J, Bruce TJ, Jones EM, Cain KD. A Review of Fish Vaccine Development Strategies: Conventional Methods and Modern Biotechnological Approaches. Microorganisms. 2019; 7(11):569. https://doi.org/10.3390/microorganisms7110569