Roth JA, Richt JA, Morozov IA (eds): Vaccines and Diagnostics for Transboundary Animal Diseases. Dev Biol
(Basel). Basel, Karger, 2013, vol 135, p 59.
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SESSION II
State of the art, progress and gaps in development of vaccines and diagnostics for high priority transboundary diseases for the NVS
Roth JA, Richt JA, Morozov IA (eds): Vaccines and Diagnostics for Transboundary Animal Diseases. Dev Biol
(Basel). Basel, Karger, 2013, vol 135, pp 61-72.
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Vaccination for the Control of Rift Valley Fever in Enzootic and Epizootic Situations
B. Dungu1, M. Donadeu1, M. Bouloy2
1 Global Alliance for Livestock Veterinary Medicines (GALVmed), Edinburgh, Scotland, UK
2 Institut Pasteur, Paris, France
Key words: Rift Valley fever, vaccines, enzootic, epizootic
Abstract: Vaccination continues to be the most effective way to control Rift Valley fever (RVF), a zoonotic insect-borne viral disease of livestock. The irregular, cyclical and persistent nature of RVF in its occurrence in enzootic situations suggests that the vaccination strategy to be considered for these regions should be different from what is envisaged for free from risk regions. Currently available RVF vaccines have been extensively used for the control of the disease. However, these vaccines have shortcomings that have encouraged many research groups to develop new vaccine candidates that would address a large number of the current challenges, and be suitable for use both in disease-free regions and in different contingency and emergency preparedness strategies. The characteristics of different RVF vaccines and vaccination strategies are discussed in this report.
INTRODUCTION
Since the first description of a Rift Valley Fever (RVF)-like disease in Kenya in 1912-1913, and the first isolation of the RVF virus in 1931 in Kenya [1], RVF continues to be a major zoonotic and economically important disease of livestock in large regions of Africa and the Middle East, where it is endemic. The disease is also considered to be a big threat to other regions of the world. Countries at risk include those adjacent or close to affected regions (such as the Middle East, Europe and North Africa), and regions further away because the virus now features on most lists of potential biological warfare agents due to its severe zoonotic nature.
RVF is a multi-species insect-borne disease caused by the RVF virus, which belongs to the Phlebovirus genus of the Bunyaviridae family. The RVF virus is enveloped and spherical with a diameter of 80-120 nm. Like all members of the family, it possesses a single stranded tripartite RNA genome composed of three segments: the large (L), the medium (M), and the small (S) segment. The L segment codes for the RNA-dependent RNA polymerase L protein; the M segment codes for the precursor of the Gn and Gc glycoproteins, and the two non-structural NSm proteins. The S segment codes for both the N nucleoprotein and the non-structural NSs protein, by using an ambisense strategy [2].
A number of factors play a role in the occurrence of outbreaks: (i) the circulation of the RVF virus through mosquito vectors; (ii) the mosquito pressure (number of breeding sites and hatching frequency), which is highly dependent on environmental conditions, particularly rainfall events; and (iii) the distribution of domestic animal hosts, essentially ruminants (goats, sheep and cattle), vulnerable to increased vector/host contacts at night. However, there is extensive species susceptibility to RVF, as set out in Table 1.
Several outbreaks have occurred since the disease was first described in Kenya. Besides those countries linked to the Great Rift Valley formation, which stretch from the Red Sea through East Africa to Madagascar, RVF has occurred in West Africa, with serious outbreaks in Egypt, Mauritania and Senegal. Some of the major outbreaks include:
ā¢ 1950-1951: Kenya; 100,000 mortality in sheep; 500,000 abortions [3];
ā¢ 1977: Egypt; 200,000 human cases, some 600 reported fatalities [4];
ā¢ 1987: Mauritania/Senegal; over 300 human deaths [5];
ā¢ 1997-1998: large outbreak in Kenya/Somalia/Tanzania: over 300 human deaths [3];
ā¢ 1998-1999: large outbreak in South Mauritania, also in Senegal;
ā¢ 2000-2001: appearance of RVF beyond the African region, in Saudi Arabia [6];
ā¢ 2007-2008: Sudan, 747 laboratory confirmed human cases, 230 deaths [7];
ā¢ 2009-2010: South Africa: 242 lab-confirmed human cases with 26 deaths (unpublished data);
ā¢ 2010: Mauritania: 63 human cases, 13 deaths [8];
Several other African countries have also reported small outbreaks or virus circulation as demonstrated by positive serology to RVF antibodies. Although several control measures have been suggested for RVF, vaccination is still the most effective tool, which should be accompanied by other measures such as effective surveillance, good diagnostic strategy and reliable emergency preparedness. This report focuses on the assessment of vaccination strategies for enzootic and epizootic situations.
Table 1: Species susceptibility to RVF [3]
CURRENT VACCINATION STRATEGIES IN ENZOOTIC REGIONS
In regions where outbreaks have occurred, the disease always seems to reoccur. Therefore, eradication or elimination in endemic regions is not a viable option at the moment. Control measures in endemic zones are aimed at early warning, emergency preparedness and minimising the impact of the disease. Measures for the prevention of the disease in regions at risk or free from RVF should be considered differently. In enzootic situations, vaccination is still the most effective method of protecting livestock. Although endemic in most of Sub-Saharan Africa, a very limited number of countries use vaccination for the control of RVF. In countries where vaccination is practiced, different approaches are used, as shown in Table 2.
Characteristics of current RVF vaccines
The advantages and disadvantages of different types of RVF vaccines are set out in Table 3. Two types of vaccines are generally utilised in countries that use vaccination for the control of RVF: live and attenuated vaccines and inactivated vaccines. The most commonly produced and used live RVF vaccines are based on the Smithburn virus derived from a strain isolated from mosquitoes in Western Uganda in 1944 and passaged 79-85 times by intracerebral inoculation of mice: this resulted in the loss of hepatotropism, the acquisition of neurotropism and the capacity to immunise sheep safely when administered parenterally [9]. The South African RVF Smithburn vaccine is based on the 103 mouse brain passage levels of the virus, while Kenya uses the 106 passage level to produce the vaccine, all in Baby Hamster Kidney anchored cell culture systems. The two major producers of the live RVF Smithburn vaccine, Onderstepoort Biological Products (OBP) in South Africa and the Kenya Veterinary Vaccines Production Institute (KEVEVAPI) have produced millions of doses since 1952 and 1960 respectively, with the vaccine having been widely used throughout Africa and the Middle East [10].
Table 2: Classification of countries based on RVF occurrence and approach to vaccination strategy
RVF Situation | Examples of countries | Current vaccination/Control strategy |
Endemic with regular outbreaks | Kenya, Tanzania, Egypt, Madagascar, Sudan | Vaccination at sign of outbreak, Egypt, Sudan: continuous/regular vaccination, No vaccination (Madagascar) |
Endemic with sporadic/reoccurring outbreaks | South Africa, Saudi Arabia, Mauritania | Continuous/yearly vaccination, No vaccination (Mauritania) |
Endemic with no large scale outbreaks (or not reported), but with serological evidence of virus circulation | Senegal, Mali, DR Congo | No vaccination |
Free high risk | Middle East, North Africa | (Active) surveillance |
Free low risk | Europe, Americas | Surveillance, talks about vaccine banks |
Table 3: Different types of RVF vaccines
The live attenuated RVF Smithburn vaccines based on the Smithburn virus have several disadvantages: they may induce abortions, malformations in the foetuses of vaccinated animals, hydrops amnii, and prolonged gestation in a proportion of vaccinated dams. Their use during an outbreak is not advised as they are based on a live virus. Since RVF outbreaks occur in irregular cycles, a number of countries do not to implement vaccination between outbreaks. Another reported problem with the live attenuated RVF Smithburn vaccine is the poor antibody response in vaccinated cattle [11].
In an attempt to address problems associated with the residual virulence of the Smithburn vaccine, as well as the poor antibody response in vaccinated cattle, an inactivated vaccine was developed and has been used since the 1970s in South Africa. This vaccine can be used in all livestock species, at different physiological stages, including pregnancy, and during outbreaks. This inactivated RVF vaccine makes it possible to vaccinate cows that can then confer colostral immunity to their offspring. Given the poor immunogenicity of this vaccine in cattle, it requires a booster three to six months after initial vaccination, followed by annual inoculations [11]. This inactivated RVF vaccine is currently produced in Egypt and in South Africa.
Since 2008, a new vaccine called RVF Clone 13 has been registered and used in South Africa. It is based on an avirulent RVF virus isolated from a non-fatal case of RVF in the Central African Republic that had been passaged in mice and Vero cells, and then plaque purified in order to study the homogeneity of virus subpopulations. A clone designated 13 did not react with specific monoclonal antibodies against NSs and when further investigated was found to be avirulent in mice, yet immunogenic [12]. This vaccine has been evaluated for safety and efficacy in sheep [13] and cattle [14]. More than 10 million RVF Clone 13 vacci...