There is a general public concern regarding emerging zoonotic diseases which has gained new relevance in the light of global warming. This is especially true regarding the spread of vector-borne diseases such CCHF, RVF and WNF.  It is, thus, imperative to work out  integrated control measures which include:

• Vector control
• Vaccination programmes
• Improved therapy strategies
• Improvement of diagnostic tools and surveillance
• Public awareness
• Capacity building and improvement of infrastructure in endemic regions

The last three aspects are parts of the work packages 2, 3 and 7.
The objectives of WP 5 is to deal with the first three measures through:

• assessment of the results of  vaccine use
• assessment of the results of vector control
• assessment of the results of different therapy strategies.
• establishment of a database for dissemination

Accordingly, this WP is divided into three tasks: Vector control, vaccination and therapy.
 

Task 1 Control of Vector

In addition to the tick and mosquito surveys, population models and climate change, the control of the vectors responsible for the transmission of the pathogens is an essential part of an integrated control measure. Accordingly, this consortium will address issues of vector control including anti-tick vaccines (in development), acaricides, and use of biological substances which have been shown to be effective against different developmental stages of the vectors.

A number of research projects have been initiated to develop cost-effective live, inactivated and molecular vaccines against both the pathogens and their vectors by different groups participating in the proposal. These studies include basic research but also practical field trials using anti-tick vaccine candidates. The CA will bring these scientists together and create realistic scenarios wherein sub-unit vaccines targeting ticks can be combined with those derived from various pathogens.

Commercial anti-tick vaccines have been developed based on recombinant BM86, used in TickGARD™ and GAVAC™,  which rely on an artificially induced immune response to internal or ‘concealed’ antigens in the tick gut of Boophilus ticks. This approach has now been used against other tick genera such as Hyalomma with encouraging results. However, the vaccine only reduces tick feeding success, rather than completely preventing the tick from feeding. Hence, better vaccine candidates are required. Another promising approach is the use of cement proteins from ticks as vaccine candidates in order to interfere with the feeding process.

A number of groups involved in this consortium are investigating the use of integrated vaccines for the vector and vector-borne pathogens. For this purpose, studies are running aiming at the identification and characterization of immunological relevant vector and pathogen antigens. The  project will create a forum for these scientists to share knowledge and elaborate scientific cooperation, particularly in areas of proteomics, traditional protein biochemistry, and molecular biology for the identification of effective delivery systems. These will enable us to create multivalent vaccines consisting of viral and vector components.
Actions will be organized to address the epidemiological impact of vaccines. It is essential that baseline evaluation and longitudinal monitoring of host- and vector-specific measures of infection incidence and challenge be undertaken, including long term post vaccination surveillance.
 

Task 2 Use of vaccines against the WNV, CCHFV and RVFV

There is no vaccines available against CCHFV and currently the following vaccines are used against WNV and RVFV:

• WNV: three vaccines are in use: whole WNV inactivated vaccine, live recombinant canary pox vaccine and a live chimera vaccine based on YF-17D.
• The presently available vaccine against RVFV is the Smithburn modified attenuated live vaccine which is currently commercialized to protect livestock. However, vaccination with the strain causes abortion or teratogenic effects in pregnant animals. A formalin-inactivated vaccine is also produced but at least two vaccination boosts are necessary for protection. Other candidates are MP12 produced by USARMRIID after in vitro mutagenesis and Clone 13 a naturally avirulent isolate for mice and sheep.

This task will analyse the current situation of the use of vaccines in order to create a database taking into account the suitability of the vaccines and the local specific situation in regions of prevalence of different virus strains. The partners involved in this consortium have great experience with the production, efficacy and safety of these vaccines under laboratory as well as field conditions. The suitability of different challenge models will be compared. Moreover, the consortium will establish a platform to discuss possibilities of using novel technologies like DIVA vaccines, subunit vaccines, genetically engineered vaccines based on reverse genetics
Despite the impact of CCHFV on human health, a safe and effective vaccine is lacking. Research on the production of vaccines against CCHFV infections in human is seriously hampered by the lack of a suitable animal model.

Taken together, a platform will be created, bringing together those CA members actively involved in molecular vaccine development, and a focus will be given to integrated vaccine strategies including pathogen and vector components and development of appropriate delivery systems.
 

Task 3 Therapy

Studies have been conducted regarding the in vivo and in vitro efficacy of ribavirin against CCHFV. It was shown that ribavirin can inhibit the viral activity, and some CCHF viral strains appeared to be more sensitive than others. The study compared the fatality rate among patients suspected of having Crimean-Congo hemorrhagic fever (CCHF) who received treatment with oral ribavirin and those who did not. Ninety-seven (69.8%) of 139 treated patients suspected of having CCHF survived, and 61 (88.9%) of 69 treated patients with confirmed CCHF survived.

The efficacy of oral ribavirin was 80% among patients with confirmed CCHF and 34% among patients suspected of having CCHF. Eight patients were given ribavirin, and all 8 survived. The study results suggested to use the ribavirin especially for the severe cases.

Concerning RVFV, ribavirin, interferon and interferon inducers (i.e.; poly-IC) were experimentally tested in RVFV infected monkeys and found to be efficient antiviral agents. However, although it was proposed to treat patients with ribavirin during the outbreak in Saudi Arabia and Yemen in 2000, to our knowledge, the drug has never been used as a treatment in patients suffering with RVF. 

For an effective therapy strategy, a working group of the CA will be liaised to WHO, who is in charge of promoting and coordinating the development of randomized clinical trials for ribavirin against CCHF. The outcome of these studies should be analysed by this working group and distributed to the partners of the project.