Stop the no. 1 elephant killer!

Normal a27bffbf95814089e4a878394108f48f0a694b46

What problem are we facing? 

Asian elephants (Elephas maximus) is considered an endangered species by the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES, http://www.iucnredlist.org/details/7140/0). The  wild Asian elephant population  is continuously being reduced due to poaching and habitat destruction. EEHV is a herpes virus unique for elephants. It may cause acute, often fatal, hemorrhagic disease (EEHV hemorrhagic disease [EEHV-HD]) in young Asian elephants (Elephas maximus), most commonly between 1 and 8 years of age. Affected elephants may peracutely die of the hemorrhagic syndrome caused by EEHV, often within 24 hours of showing initial clinical signs of illness.1,15 A vaccine or effective antiviral treatment is not available. For zoo veterinarians, this disease may be one of the most challenging and daunting aspects of caring for a breeding elephant herd. Based on May 2017 population numbers, EEHV-HD was the cause of 53% of deaths in all Asian elephants born in North America since 1980, making it the single greatest cause of death in this cohort. In Europe, 43 out of more than 200 Asian elephants born since 1995,diedof which 60%  (26) due to EEHV-HD.In fact,  the largest cause of death in Asian elephants in the last decades.similar to the situation in the USA .

Much remains to be learned about the impact of EEHV on the estimated 15,000 captive Asian elephants and greater than 40,000 wild elephants across Asia. During the First and Second Asian EEHV Strategy Meetings in 2015 and 2016, more than 80 cases of EEHV-HD were identified in captive Asian elephants in  Asian elephant range countries (Thailand, India, Cambodia, Indonesia, Myanmar, Nepal, Sabah, Borneo, Laos, and Peninsular Malaysia), with less than 5 elephants surviving EEHV-HD. Research in these countries have demonstrated that EEHV is also a serious concern in wild elephants: more than 120 fatal EEHV-HD cases in wild Asian elephants have been recorded since 2003, based on gross necropsy reports and PCR. Wildlife veterinarians in some countries suspect much higher losses due to EEHV but are limited in their ability to confirm cases due to lack of diagnostic assays and laboratories. EEHV has caused disease in African elephants as well, and more research is needed to better understand the epidemiology in this species. The impact of EEHV on African elephants, both on free-ranging and domesticated  populations remains largely unknown.

Healthy Asian and African elephants have been shown to shed one or multiple types of EEHV as part of a natural infection cycle. Based on current research, all adult elephants appear to carry and shed one or more EEHV strains and/ or species intermittently and asymptomatically. So far 8 EEHV subtypeshave been identified.Applying known herpesvirus biology to EEHV,  tells us that all adult elephants must have survived an episode of EEHV exposure and viremia at some point in their lives and are now latent carriers of the virus.Elephants ill from EEHV-HD can be viremic up to 2 weeks prior to the onset of clinical signs.22During this time, the virus may be detected via whole blood quantitative PCR. While this is the best way to detect emerging EEHV-HD early, this had not yet lead to an effective treatment of EEHV-HD.

What do we want to do?  

Within the project we aim to develop the following:

  1. An EEHV vaccine and insight into cross-protection provided against different types and subtypes
  2. EEHV diagnostic serological assays, differentiating between types and subtypes as well as between natural infection and vaccination (DIVA)
  3. Increasedinsight into pathogenesis of EEHV in both Asian and African elephants , which may lead to immunomodulatory intervention in acute cases and to improvedantiviral therapy?

Differential pathogenesis due to different EEHV (sub-)types

Optional, for the long term, we aim to protect zoo elephants against EEHV-HD and to provide insight into the burden of infection/disease of EEHV in wild Asian and African elephants

 

There is an urgent need for effective treatment options of EEHV-HD. For the long term there is not only a need for an EEHV vaccine, but also for tools with which this virus and the disease it causes may be studied (pathogenesis, epidemiology, diagnosis). The proposed research aims to tackle these issues.

Research strategy

  1. Expression of EEHV envelope glycoproteins of different subtypes in 293T cells. Focus on Gb and gD
  2. Generation of polyclonal and monoclonal antibodies to both cytokine and virus (sub)types (rec antigen) specific
  3. Development of serological assays (ELISA and/or IFA-based)for both cytokines and viruses, In addition assessment of application of IGRA as a diagnostic assay for virus infection
  1. Apply antibodies to study postmortem samples (increased insight into pathogenesis in collaboration with Pathobiology)
  2. Apply antibodies to study antigenic relationship between EEHV
  3. Apply serological assays for epidemiological screening of captive and domesticated elephants in a multinational study
  4. Apply antibodies to assess the impact of various cytokines in the acute fase of disease
  5. Select antigens for the generation of EMCV-basedEEHV vaccine
  6. Analyze immunogenicity of vaccine in small animal model
  7. Apply vaccine in Zoo elephants?
  8. Serosurvey of both Asian and African wild elephant populations for EEHV (sub)type infection

 

What do we hope to achieve? 

At least 60% of young elephants- (up to 8 years) die are due to EEHV, hence our efforts will contribute to sustain a vital Asian elephant  population  Captive elephant populations are considred vital to the future of Asian elephants in their original habitat, as their numbers are declining rapidly. Habitat destruction and poaching cause fragmentation of existing wild elephant herds jeopardizing the reproduction in the wild. It is expected that within the next 20-30 years, captive elephants will be released in protected areas where the number of wild elephants have been reduced to unsustainable numbers.

The killer virus

Asian elephants (Elephas maximus) is considered an endangered species by the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES, http://www.iucnredlist.org/details/7140/0). The  wild Asian elephant population  is continuously being reduced due to poaching and habitat destruction. EEHV is a herpes virus unique for elephants. It may cause acute, often fatal, hemorrhagic disease (EEHV hemorrhagic disease [EEHV-HD]) in young Asian elephants (Elephas maximus), most commonly between 1 and 8 years of age. Affected elephants may peracutely die of the hemorrhagic syndrome caused by EEHV, often within 24 hours of showing initial clinical signs of illness.1,15 A vaccine or effective antiviral treatment is not available. For zoo veterinarians, this disease may be one of the most challenging and daunting aspects of caring for a breeding elephant herd. Based on May 2017 population numbers, EEHV-HD was the cause of 53% of deaths in all Asian elephants born in North America since 1980, making it the single greatest cause of death in this cohort. In Europe, 43 out of more than 200 Asian elephants born since 1995,diedof which 60%  (26) due to EEHV-HD.In fact,  the largest cause of death in Asian elephants in the last decades.similar to the situation in the USA .

 

The impact of EEHV

Much remains to be learned about the impact of EEHV on the estimated 15,000 captive Asian elephants and greater than 40,000 wild elephants across Asia. During the First and Second Asian EEHV Strategy Meetings in 2015 and 2016, more than 80 cases of EEHV-HD were identified in captive Asian elephants in  Asian elephant range countries (Thailand, India, Cambodia, Indonesia, Myanmar, Nepal, Sabah, Borneo, Laos, and Peninsular Malaysia), with less than 5 elephants surviving EEHV-HD. Research in these countries have demonstrated that EEHV is also a serious concern in wild elephants: more than 120 fatal EEHV-HD cases in wild Asian elephants have been recorded since 2003, based on gross necropsy reports and PCR. Wildlife veterinarians in some countries suspect much higher losses due to EEHV but are limited in their ability to confirm cases due to lack of diagnostic assays and laboratories. EEHV has caused disease in African elephants as well, and more research is needed to better understand the epidemiology in this species. The impact of EEHV on African elephants, both on free-ranging and domesticated  populations remains largely unknown.

 

Healthy Asian and African elephants have been shown to shed one or multiple types of EEHV as part of a natural infection cycle.. Based on current research, all adult elephants appear to carry and shed one or more EEHV strains and/ or species intermittently and asymptomatically. So far 8 EEHV subtypeshave been identified.Applying known herpesvirus biology to EEHV,  tells us that all adult elephants must have survived an episode of EEHV exposure and viremia at some point in their lives and are now latent carriers of the virus.Elephants ill from EEHV-HD can be viremic up to 2 weeks prior to the onset of clinical signs.22During this time, the virus may be detected via whole blood quantitative PCR. While this is the best way to detect emerging EEHV-HD early, this had not yet lead to an effective treatment of EEHV-HD.

 

What we want to do 

Within the project we aim to develop the following: 

  1. An EEHV vaccine and insight into cross-protection provided against different types and subtypes
  2. EEHV diagnostic serological assays, differentiating between types and subtypes as well as between natural infection and vaccination (DIVA)
  3. Increasedinsight into pathogenesis of EEHV in both Asian and African elephants , which may lead to immunomodulatory intervention in acute cases and to improvedantiviral therapy?

Differential pathogenesis due to different EEHV (sub-)types

Optional, for the long term, we aim to protect zoo elephants against EEHV-HD and to provide insight into the burden of infection/disease of EEHV in wild Asian and African elephants

 

How we are going to do it 

There is an urgent need for effective treatment options of EEHV-HD. For the long term there is not only a need for an EEHV vaccine, but also for tools with which this virus and the disease it causes may be studied (pathogenesis, epidemiology, diagnosis). The proposed research aims to tackle these issues.

 

Research strategy

  1. Expression of EEHV envelope glycoproteins of different subtypes in 293T cells. Focus on Gb and gD
  2. Generation of polyclonal and monoclonal antibodies to both cytokine and virus (sub)types (rec antigen) specific
  3. Development of serological assays (ELISA and/or IFA-based)for both cytokines and viruses, In addition assessment of application of IGRA as a diagnostic assay for virus infection
  4. Apply antibodies to study postmortem samples (increased insight into pathogenesis in collaboration with Pathobiology)
  5. Apply antibodies to study antigenic relationship between EEHV
  6. Apply serological assays for epidemiological screening of captive and domesticated elephants in a multinational study  
  7. Apply antibodies to assess the impact of various cytokines in the acute fase of disease
  8. Select antigens for the generation of EMCV-basedEEHV vaccine
  9. Analyze immunogenicity of vaccine in small animal model
  10. Apply vaccine in Zoo elephants?
  11. Serosurvey of both Asian and African wild elephant populations for EEHV (sub)type infection

 

 

What's the impact? 

As mentioned in introduction 60% of young elephant- (up to 8 years) death are due to EEHV, hence our efforts will contribute to sustain a vital Asian elephant  population  Captive elephant populations are considred vital to the future of Asian elephants in their original habitat, as their numbers are declining rapidly. Habitat destruction and poaching cause fragmentation of existing wild elephant herds jeopardizing the reproduction in the wild. It is expected that within the next 20-30 years, captive elephants will be released in protected areas where the number of wild elephants have been reduced to unsustainable numbers.