Development of an efficient veterinary rabies vaccine production process in the avian suspension cell line AGE1.CR.pIX

Abstract

Background Mass vaccination of dogs as important rabies reservoir is proposed to most effectively reduce and eliminate rabies also in humans. However, a minimum coverage of 70% needs to be achieved for control of the disease in zoonotic regions. In numerous developing countries, dog vaccination rate is still dangerously low because of economic constraints and due to a high turnover in dog populations. Improved vaccine production processes may help to alleviate cost and supply limitations. In this work, we studied and optimized the replication and vaccine potency of PV rabies virus strain in the muscovy-duck derived AGE1.CR and AGE1.CR.pIX suspension cell lines. Results The BHK-21-adapted PV rabies virus strain replicated efficiently in the avian cell lines without requirement for prior passaging. CR.pIX was previously shown to augment heat shock responses and supported slightly higher infectious titers compared to the parental CR cell line. Both cell lines allowed replication of rabies virus also in absence of recombinant IGF, the only complex component of the chemically defined medium that was developed for the two cell lines. After scale-up from optimization experiments in shake flask to production in 7-l bioreactors peak virus titers of 2.4 × 108 FFU/ml were obtained. The potency of inactivated rabies virus harvest according to the NIH test was 3.5 IU/ml. Perfusion with the chemically defined medium during the virus replication phase improved the potency of the vaccine twofold, and increased the number of doses 9.6 fold. Conclusion This study demonstrates that a rabies vaccine for animal vaccination can be produced efficiently in the AGE1.CR.pIX suspension cell line in a scalable process in chemically defined medium.

30-Year Development of Inactivated Virus Vaccine in China

“…Currently, Vaccitech in Britain has utilized AGE1.CR.pIX to develop the universal influenza A vaccine MVA-NP + M1 [64]. Research by Trabelsi et al [65] indicates that in the AGE1.CR.pIX suspension cell line, the use of chemically defined media can effectively produce a scalable process for rabies vaccine intended for animal use. EB66 ® , developed by Valneva in France, originates from duck embryo cells and exhibits sensitivity to influenza, measles, mumps, and poxviruses.…”

Seed Train Optimization in Microcarrier-Based Cell Culture Post In Situ Cell Detachment through Scale-Down Hybrid Modeling

“…Many manufacturers rely on static culture methods, such as roller bottles or multilayer culture systems, for cell propagation and final antigen manufacturing [ 7 , 8 , 9 ]. Rotarix ® , Varivax ® , Meruvax [ 9 ], Ervebo ® [ 10 ], PRRS [ 11 ], and rabies vaccines [ 12 ] for pigs are examples of the vaccines produced with static culture methods. However, these methods come with drawbacks, including restricted inoculation, limited monitoring of process parameters, substantial manufacturing space requirements, workforce limitations, and limited production scale.…”

The potential for the double risk of rabies and antimicrobial resistance in a high rabies endemic setting: detection of antibiotic resistance in bacterial isolates from infected dog bite wounds in Uganda

“…It is also estimated that the country would experience approximately 592 deaths due to rabies in the absence of PET [ 6 ]. In such low-income countries with endemic dog-transmitted human rabies, pre-exposure prophylaxis (PrEP) with rabies vaccine is almost unavailable and dog vaccination coverage is low [ 7 , 8 ]. This means that dog bite injuries carry with them a high risk for rabies.…”