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Following the vaccine that wiped out rinderpest, a new vaccine against sheep and goat plague proves promising


A Tunisian man carries a sheep suffering from peste des petits ruminants (PPR), also known as sheep and goat plague, a highly contagious animal disease affecting small ruminants. Once introduced, the virus can infect up to 90% of an animal heard and the disease kills anywhere from 30 to 70% of infected animals (photo credit: AgriMaroc [Marrakech]–DR).

Vaccines can lose their potency and become ineffective when being stored or transported. This problem adds to the cost of vaccines and limits their availability. What’s needed, particularly in tropical regions with poor infrastructure and hot and variable climates, are vaccines that can withstand storage or shipment at changing and/or high temperatures.

Keeping vaccines in a narrow band of acceptable temperatures during shipment is challenging and expensive—the ‘cold chain’ consumes about 80 percent of the total cost of vaccination programs according to the U.S. National Sciences Foundation (NSF). . . .

The World Health Organization (WHO) estimates that nearly 50% of lyophilized (freeze-dried) and 25% of liquid vaccines are wasted each year. One of the biggest contributors to this wastage is disruption of the cold chain. . . .

Large public health organizations, including the Bill and Melinda Gates Foundation, have long advocated for innovations that will enable the development of more stable vaccines. However, the challenges of developing thermostable vaccines have been greater than expected.

VBI Vaccines

A new paper, A thermostable presentation of the live, attenuated peste des petits ruminants vaccine in use in Africa and Asia, by researchers at the International Livestock Research Institute (ILRI) describes development of a thermostable version of the current, effective vaccine against ‘peste des petits ruminants’, or PPR for short, a disease more commonly known as sheep and goat plague.

From the Abstract
‘The research objective was to develop a thermostable vaccine against peste des petits ruminants (PPR), a morbilliviral disease of small ruminants targeted for eradication that is a major constraint on the livelihoods of the rural poor throughout much of Africa and Asia. Although existing PPR vaccines provide life-long immunity, they require continuous refrigeration. This limits their utility in developing countries.

‘Methods for the lyophilization of a related morbillivirus, rinderpest (RP), resulted in vaccine that could be used in the field for up to 30 days without refrigeration which was a major contribution to the global eradication of RP completed in 2011. The present research applied the rinderpest lyophilization method to the attenuated Nigeria 75/1 PPR vaccine strain, and measured thermostability in accelerated stability tests (AST) at 37 °C. . . .

‘Vaccines produced using LS and the rinderpest method of lyophilization were the most stable . . ., [possessing] sufficient thermostability for use without a cold chain for up to 30 days which will greatly facilitate the delivery of vaccination in the global eradication of PPR.’

From the Introduction

Peste des petits ruminants (PPR) is a highly contagious, acute viral disease that primarily affects domestic small ruminants associated with high mortality and severe socio-economic impact.

‘The disease is caused by the virus of the genus Morbillivirus, which includes rinderpest (RP), measles, and canine distemper and the phocid distemper viruses. The clinical symptoms associated with the disease in small ruminants are pyrexia, oculo-nasal discharge, stomatitis, pneumonia and diarrhoea. The apparent range of PPR has expanded in recent years to include parts of North Africa, sub-Saharan Africa as far south as Zambia, the Middle East, Central and South Asia. In late 2013, the disease entered China for the second time with 244 outbreaks from across China reported to the World Animal Health Organization by June 2014.

‘Small ruminants play an important role in the livelihoods of many livestock economies. They play a greater role in household food security than large ruminants and are more easily marketed to meet immediate cash needs.

PPR is often ranked as one of the top two or three disease constraints to small ruminant production.

International recognition of the pivotal role of PPR in the livelihoods of the poor has led to increasing recognition of the need for a globally coordinated eradication program.

Lessons from the global eradication of RP completed in 2011, a close relative of PPR, suggest that PPR eradication is an achievable and appropriate goal.

From the Discussion
‘This goal of this work was to compare different approaches to thermostabilizing PPR vaccine and document PPR vaccines that were suitable for commercialization and use without a cold chain. Thermostability is a relative term referring the rate of degradation as a function of temperature. Virtually all substances degrade and degradation or change is accelerated by increased temperature. For the purposes of this discussion we define thermostability as the ability of the product to retain the required minimum dose at ambient temperatures for a period of time that facilitates practical fieldwork without a cold chain. In the case of rinderpest, 30 days was found to be sufficient for teams to work on the field without a cold chain. . . . The product must be able to resist average ambient temperature and temperature fluctuations for a defined period with a wide margin of safety. . . .

‘The rinderpest method of thermostabilization stabilized the PPR vaccine virus to practical levels equivalent to those obtained with rinderpest. This was to be expected given that thermostabilization in physico-chemical process and that all the morbillivirus are essentially identical at the structural level. The vaccine has suitable stability for use without a cold chain for up to 30 days. As with rinderpest, this is sufficient stability for vaccination teams to travel in the field without refrigeration or ice. . . .

‘In addition to reducing the need for cold chain infrastructure, this level of stability frees vaccination programs from the requirement for vehicles, which together with per diem is the principal cost of vaccine delivery and vaccination as a whole. It also facilitates the integration of community-based vaccination programs that are critical to obtaining good herd immunity levels and extending the reach of livestock health and disease eradication programs to remote and politically unstable areas. . . .

As with rinderpest, the next step for PPR should be to adapt production to commercial scale lots and pilot the use of the vaccine in practical field programs.

From the Conclusion
‘The method used in the lyophilization of thermostable RP vaccine and a lactalbumin and sucrose stabilizer when applied to PPR vaccine resulted in a vaccine with levels of thermostability that were comparable to those obtained with RP and superior to the other options tested with PPR vaccine virus. This level of thermostability is sufficient for use in the field without a cold chain for up to one month, as was done in the global eradication of RP.’

The rinderpest method of thermostabilization has been successfully commercialized in the past indicating that the commercialization of thermostable PPR vaccine using the rinderpest method is feasible and can greatly facilitate the eradication of PPR.

Acknowledgements
This work was supported by the Australian Government Department of Foreign Affairs and Trade (DFAT) through a collaboration between the BecA-ILRI Hub and Australia’s Commonwealth, Scientific and Industrial Research Organisation (CSIRO). The work also received support from the ILRI-led CGIAR Research Program on Livestock and Fish and the CGIAR Fund Donors.

More information
Read the whole paper in Vaccine: A thermostable presentation of the live, attenuated peste des petits ruminants vaccine in use in Africa and Asia, by Jeffrey Mariner, James Gachanja, Sheltone Tindih and Philip Toye, International Livestock Research Institute, 27 Jun 2017.

Read previous ILRI articles on the eradication of rinderpest and development of a thermostable PPR and other livestock vaccines.

 

 

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