Session III: Vaccine security and critical resources for emergency management.
Aim: to compare national and regional approaches to ensure sufficient critical resources in FAST crises, including quality vaccines and diagnostics, to ensure proper response during multi-country epidemics.
15 DECSESSION III
1 Department of Agriculture, Water and the Environment GPO Box 858, Canberra ACT 2601, Australia
Decisions to invest in resources to prepare for transboundary animal disease emergencies are challenging. In countries like Australia where outbreaks of transboundary animal diseases occur infrequently, it may not be cost-effective to pre-emptively employ large numbers of personnel and invest in stockpiles of material. This presentation will review Australia’s 25-year program of epidemiological modelling for transboundary diseases. It will also discuss examples where epidemiological modelling, simulation exercises and performance assessments/standards have been used to guide contingency planning, investment in vaccine banks, laboratory management in emergencies, and surveillance for diseases such as foot and mouth disease, highly pathogenic avian influenza and equine influenza.
M. McElroy, J. Connell, S. Coughlan, M. Keogan
1 DAFM Laboratories, Backweston, Celbridge, Co. Kildare, Ireland. W23 VW2C
2 NVRL, University College Dublin, Belfield, Dublin 4, Ireland.
3 Enfer Labs, Unit T, M7 Business Park, Newhall, Naas, Co. Kildare, Ireland.
4 HSE National Clinical Programme for Pathology, Beaumont Hospital, Dublin 9, Ireland
During the COVID-19 pandemic, animal health laboratories have assisted the public health authorities in many countries in increasing national molecular testing capacity and in developing other diagnostic capabilities for SARS-CoV-2.
In Ireland, the Department of Agriculture Food and the Marine (DAFM) Laboratories has worked closely with the National (human) Virus Reference Laboratory (NVRL), a private animal health laboratory (Enfer Labs) and the Health Services Executive (HSE) over the course of this pandemic.
In the early months after the first diagnosis of COVID-19 in Ireland, these efforts were focused on adapting laboratories and molecular testing capability ordinarily used for animal disease control programmes, to testing human clinical specimens for SARS-CoV-2 RNA.
Recently, the focus of this “One Health” collaboration has changed from laboratory-based SARS-CoV-2 RNA testing to the application and evaluation of rapid detection methods for SARS-CoV-2 antigen in specific high-risk settings for COVID-19 such as meat processing plants.
Supply chain issues, specifically the availability of reagents for automated extraction of nucleic acids, was a limiting factor and a challenge in national efforts to scale up molecular testing capacity during the first half of 2020. On the flip side, the large number of rapid test kits for SARS-CoV-2 antigen that have recently come to market, with the main advantage of detecting those individuals who are probably infectious. However they present a different type of challenge for public health authorities – how to quickly assess and select the most appropriate test kits for different purposes in a fair, objective and robust manner that complies with public procurement guidelines and to prove their application in “real world” situations. While verification and validation methodologies to compare tests are well established, comparison of testing strategies is more challenging.
Michael James Francis
*Managing Director, BioVacc Consulting Ltd, The Red House, 10 Market Square, Amersham, HP7 0DQ, UK.
Email: firstname.lastname@example.org, Website: www.biovacc.com
This Keynote Presentation will describe the veterinary vaccine development process. It will cover steps from bench to field and go on to discuss a few ways in which the standard process can potentially be accelerated. It will then briefly review novel vaccine platform technologies and provide an example of a “One Health” approach to vaccination.
Veterinary Vaccine Development Process and Accelerated Development
Different stages of the commercial development process will be presented from new product considerations and early discovery through to feasibility, full development and product registration (www.vaccinedevelopment.org.uk). A few potential ways in which this process could be accelerated will then be discussed with specific reference to the research & development, manufacturing and regulatory stages.
Platform Technologies and a “One Heath” vaccine
A selection of recombinant vaccine platform technologies covering killed/inactivated and live/attenuated approaches will be briefly reviewed and an example of a “One Health” approach to Rift Valley Fever vaccination utilizing a ChAdOx1 non-replicating virus vector will be presented. This will include data on the safety, efficacy and stability of the vaccine and a summary of some of the unique attributes of this novel platform technology for use in both livestock and humans. The significance of new vaccine technologies within veterinary medicine will be discussed and some biotechnology breakthroughs that have occurred within veterinary vaccines will be reviewed.
Finally, a few key messages related to future veterinary vaccine development will be covered and this summary will include market considerations, commercial requirements, end-user benefits and the importance of novel technologies.
The VPH Center of Boehringer-Ingelheim
Vaccine security is not guaranteed when quality vaccines are not available to serve the demand in due time. This is often the case for some products like FMD vaccines, for which sales forecasts are unreliable, sudden peaks in demand can occur because of outbreaks, and there is a lack of inventory at the manufacturers’. This situation could be addressed by the constitution of banks, which are a unique business model well suited to address sudden and unplanned surges in demand for vaccine.
Banks have been established at least for FMD, Bluetongue, rabies, PPR, LSD and avian influenza vaccines. Banks can made of antigen, which then has to be formulated into vaccine by the manufacter, or of vaccine stocks.
Today the FMD antigen bank model is mostly used by FMD-free countries, as an insurance against an outbreak on their territory. Initiatives are ongoing to mutualize efforts and put in place shared banks, even though allocation rules are often difficult to set.
Banks are also a good model for endemic countries, not only to absorb sudden surges in demand, but also as a trigger for externally-funded pilot vaccination campaigns to demonstrate their benefits. With the support of international organizations, countries could be incentivized to put in place the proper infrastructure for vaccination, which will then make their control programs sustainable.
Amin S. Asfor
Madeeha Afzal, Anna B. ludi, Alison Burman1 and Donald P. King
1 The Pirbright Institute, Ash Road, Pirbright, Surrey, GU24 0NF, UK.
AVAILABLE UPON REQUEST
The gold standard test to assess post vaccination responses is the virus neutralisation test (VNT). The use of VNT is constrained by the need for high containment facilities, well trained staff and the time taken to prepare cells and reagents. In contrasts to the high inter serotype-specificity of the VNT, the structural protein ELISA suffer from low serotype-specificity. Development of simple, specific tests, such as a peptide ELISA, that mimic the measurement of neutralising antibodies could offer an attractive approach to measure post-vaccination responses.
Materials and methods
An indirect ELISA using a synthetic peptide (PPR LTD, UK) representing the site 1 on the G-H loop of FMDV serotype O as antigen was developed and optimised. Initial validation on monovalent serotype O sera (n = 5) and known inter-serotypic cross-reactive monovalent serotype A sera (n= 5) has been carried out. A correlation between the peptide ELISA and the VNT titre was performed using GraphPad Prism version 8.
The G-H loop peptide was able to specifically react with homologous sera without inter-serotypic cross reactivity with the monovalent serotype A sera despite the cross-reactive response seen with these sera in other ELISA formats. Within serotype O, the sera from different animals vaccinated or infected with different serotype O strains varied in its reactivity to the peptide, emphasising that this variation could be due to sequence variation at the fingerprints of the epitope used or due to quantitative differences in the neutralising antibody level as measured by VNT which correlate to certain extent with the OD values.
The preliminary data suggests that the G-H loop peptide could be a surrogate model for detecting specific neutralising antibodies that might correlate with VNT titres and overcome the cross reactivates observed in other ELISA platforms. More in-depth validation with different serotypes needs to be carried out. One limitation of this approach could be the detection of only a fraction of the total neutralising antibody response is measured, since the assay only targets one out of five known neutralising antigenic sites of FMDV.
AVAILABLE UPON REQUEST
Maud Marsot, Durand Benoit, Wafa Ben Hammouda, Heni Hadj Ammar, Malek Zrelli2and
1 University Paris Est, ANSES, Laboratory for Animal Health, Epidemiology Unit, Maisons-
2 Tunisian Veterinary Services, 30 rue Alain Savary, 1002 Tunis, Tunisia
Foot and mouth disease (FMD) is a highly contagious viral disease that affects domestic and wild artiodactyl animals and causes considerable economic losses related to outbreak management. In Tunisia, the last FMD outbreak took place in 2018-2019. The effectiveness of control measures implemented against FMD depends, in particular, on the human resources used to implement them. The main aim of this study was to determine and compare the necessary and available human resources to control FMD outbreaks in Tunisia using emergency vaccination and assess whether there was a gap. To do this
Materials and methods
We developed a reference grid of necessary human resources for the management of one FMD-infected premise in Tunisia. Field surveys, conducted in the 24 governorates of Tunisia, allowed quantifying the available human resources for each category of skill considered in the reference grid. For each governorate, we then compared available and necessary human resources to implement vaccination according to eight scenarios mixing global or cattle-targeted vaccination and different levels of human resources.
The comparison of available and necessary human resources showed vaccination-related tasks to be the most time-consuming in terms of managing an FMD outbreak. Increasing the available human resources using appointed private veterinarians allowed performing the emergency vaccination of animals in the governorate in due time, especially if vaccination was targeted on cattle.
This study was carried out in the context of a changing animal health sector in Tunisia, due to discussions on the reform of veterinary services, it could provide support to the authorities and an inventory of the human resources that could be mobilized to properly adapt and optimize the control strategy in the event of a FMD outbreak in Tunisia. The reference grid developed here could be used by the governorates to help authorities properly prepare for a potential FMD outbreak.
B. Vosough Ahmadi, N. Lyons, P. Motta
1 The European Commission for the Control of Foot and Mouth Disease, Food and Agricultural Organisation for the United Nations
Foot-and-mouth disease (FMD) is caused by a picornavirus, affecting cloven-hoofed animals. It is recognized to have large economic impacts due to reduced productivity, food security and access to international trade. Vaccination against FMD is a significant part of any endemic country’s control strategy as it aims to reduce clinical disease and transmission from infected livestock. However, there is often a supply and demand mismatch with the FMD vaccine. There are several factors contributing to this, including limited information on current and future vaccine doses a country requires for their control strategy. Quantification of the size of the FMD vaccine demand, particularly in endemic settings, is therefore of increasing importance.
Material & Methods
A quantitative modeling approach was developed considering indicators of increasing demand, such as estimated growth of livestock populations and progress of disease control policy linked to the projected FMD Progressive Control Pathway (PCP) stage. The model is a stochastic one written in R language. The OIE WAHIS database was used along with experts’ opinion, sought by designing and implementing a Delphi study, to determine the extent of vaccine coverage as well as the reduction in number of outbreaks for each PCP stage. The model splits vaccine demand into two categories; prophylactic vaccination and reactive vaccination. Predicted vaccine doses were then calculated using country specific data on current FMD outbreaks, livestock population and density.
Full model descriptions and preliminary results will be presented in the OS20 session.
Further development of this tool will be conducted to increase accuracy of the vaccine dose numbers and identify the most cost-effective investments in quality vaccine production. This model will provide support to the global efforts against FMD by providing projected estimates about FMD vaccine demand at national and global levels in the upcoming year.
P Jansen van Vuren, W Vosloo
1 Commonwealth Scientific and Industrial Organisation, Australian Centre for Disease Preparedness, Geelong, Australia
Pigs play an important role in the epidemiology of FMD in endemic countries where the species is abundant. In disease free countries, the virus amplifier role of pigs is a concern, should an incursion occur. Although vaccination is an option, improved tools are required to measure immune responses and predict correlates of protection. Previous results have shown that the intradermal (ID) vaccine delivery route provides comparable protection as compared to intramuscular (IM) vaccination, without causing local granulomatous reactions at the site of vaccination. We aimed to compare the immunological outcome of the different routes of vaccine delivery using a Systems Immunology (SI) based approach to analyse the transcriptomic data by studying the differentially expressed genes in peripheral blood mononuclear cells (PBMCs).
Materials and Methods
Groups of pigs (Sus scrofa domesticus) received a prime only IM or ID monovalent vaccination and blood was collected 3 days prior and 3 days post vaccines (dpv). PBMCs were isolated and messenger RNA sequenced. Transcribed genes were grouped according to biological function in the context of known Blood Transcriptome Modules (BTMs).
Although there were no detectable FMDV-specific antibody responses in either of the two vaccine groups at 21 and 28 dpv, there was a notable difference in the extent to which the two vaccination routes modulated innate and adaptive immune responses. IM and ID vaccination promoted BTM families involved in natural killer and T-cell differentiation, activation, signalling, co-stimulation and proliferation. ID vaccination further positively modulated dendritic cell antigen processing, presentation and activation; type I interferon response; and inflammatory responses and complement activation. Interestingly B-cell development and differentiation, B-cell receptor signalling and immunoglobulins were negatively modulated in both groups when comparing 3 day post- and pre-vaccination gene expression.
The novel SI approach provides a tool to measure the early immune responses in vaccinated pigs, before antibodies are detected. Expansion of this work is required to correlate the detection of these early responses to booster vaccination and downstream protection from challenge.
1 The Pirbright Institute
2 The European Commission for the Control of Foot-and-Mouth Disease (EuFMD)
Scoping work was carried out to gather information on the state of preparedness for emergency vaccination for FAST diseases in EuFMD Member Nations (MN); and on the issues that constrain them from inclusion of vaccination in their plans. Different aspects of emergency vaccination were investigated including vaccination strategies, access to vaccines and operational preparedness. The scope of the work was category 1 FAST diseases which is Foot- and- Mouth Disease (FMD), Lumpy Skin Disease (LSD), Peste des Petits Ruminants (PPR) and Sheep and Goat Pox (SGP).
Materials and methods
An online questionnaire was sent out to 39 EuFMD member nations plus three additional European countries. The online tool SurveyMonkey® was used and the data was analysed using R. The questionnaire was aimed at risk managers/ contingency planners.
The response rate was 15 out of 42 countries. Some examples of preliminary key findings were that the level of planning for emergency vaccination is higher for FMD than PPR and SGP, many of the responding countries rely on the EU bank with no other arrangements to source vaccines, not all countries have a system to perform a rapid evaluation and approval of vaccines for emergency use, a relative high number of member nations would choose a vaccinate-to-cull strategy over a vaccinate-to-live strategy for FMD and over 50% of countries have an exit plan for FMD but only one country has stated they have an exit plan for PPR or SGP.
The questionnaire result will be followed up by semi-structured group interviews with EuFMD MNs risk managers/ contingency planners to validate the results and to capture more detailed information on the gaps and needs in MNs.
Merck Animal Health, USA
The often-accepted approach to FMD vaccination campaigns is that it is important to vaccinate as many animals as possible against as many strains as may occur in the country. However, this approach is subject to resource limitations. For instance, with constrained budget then cheaper, low quality vaccines may be purchased, or with the limited veterinary manpower then unskilled operatives may be used.
Modelling shows that high quality vaccines will eliminate disease quicker than low quality vaccines and is cost effective. Prioritization is therefore imperative, but first we need to understand what prioritization means as this can take different forms. Once we have defined prioritization then two elements become key, one is the understand of where the disease is occurring, ie surveillance, and the other is predicting need, ie forecasting.
Finally we can consider examples of prioritization such as the focus on areas where the greatest spread may occur or targeting the strain most likely to be of current risk.
The goal of all players is to control FMD as quickly as possible to reduce the impact of the disease and to remove the risk to disease free areas. Prioritization of vaccine usage is an important component in achieving that goal. During this talk we highlight these points and open the discussion on how best to implement these approaches.
L. Quiroz, P. Hullinger
1 Emergency Preparedness and Response Section, Animal Health Branch – AHFSS, California Department of Food and Agriculture.
2 The European Commission for the Control of Foot-and -Mouth-Disease, Food and Agriculture Organization, Rome, Italy.
The goal of an emergency FMD vaccination campaign is to suppress virus replication in high-risk susceptible animals by rapidly vaccinating a high proportion (≥85%) of the at-risk population. The selected vaccination strategy will dictate the disposition of vaccinated animals, which may be euthanasia/disposal, slaughter for consumption, or living out useful lives, or any combination of these. Preparing for such a vaccination campaign, through developing a response/implementation plan and procedures, is essential.
Materials and methods
The California FMD Vaccination Plan involves a multi-disciplinary group with the appropriate authority and FAD response expertise. This group will consider outbreak characteristics and advise the State Animal Health Official as to whether emergency vaccination is warranted.
According to the current plan, California will receive, sort, store, maintain cold chain, distribute vaccine and maintain appropriate animal ID, tracking and documentation associated with the vaccination campaign. The location of the state vaccine warehouse will be as close as practical to where the vaccine is to be deployed, but outside control areas. Vaccine storage and handling requirements are stipulated in the state’s FMD Vaccination Plan and the National Veterinary Stockpile Plan.
To effectively implement a responsive FMD vaccination plan in a timely manner requires significant preplanning. Other elements requiring further planning and standardization include animal identification standards and requirements for tracking vaccinated animals/movement permits, tracking required for animal products derived from vaccinates, standards for employing third part logistics companies to support vaccine handling and distribution, and prioritizing amongst animal populations when vaccine is scarce.
Emikpe B.O., Shoyinka S.V.O., Bodjo C.S., Nwankpa N., Sabri M.Y
1 Department of Veterinary Pathology and Microbiology, University of Nigeria, Nsukka. Enugu State, Nigeria.
2 Department of Veterinary Pathology, University of Ibadan, Ibadan, Oyo State, Nigeria.
3 Clinical Pathology Laboratory, Faculty of Veterinary Medicine Teaching Hospital, University of Nigeria, Nsukka, Enugu State, Nigeria.
4 African Union Pan-African Veterinary Vaccine Centre, Debre-Zeit, Ethiopia.
5Department of Veterinary Pathology, Universiti Putra Malaysia, Serdang, Malaysia.
Introduction: Intranasal administration of Peste des petits ruminants (PPR) vaccine as a potentially effective means for mass vaccination has been experimentally demonstrated to induce strong mucosal and systemic immune responses in goats. However, little is known about the influence of intranasal PPR vaccination application methods on the induction of immune response in goats. This study compares the influence of two different intranasal vaccine application methods on the immune responses in goats.
Materials and methods: Twenty, male, PPR immunologically naive West African dwarf goats were divided into four groups (n=5). Groups A and B were vaccinated intranasally (IN) with live attenuated PPR vaccine (Nigeria 75/1) by either nasal dropper (Group A) or nasal spray (Group B) methods and compared with the subcutaneous route vaccination (Group C) and unvaccinated control (Group D) for 28 days.
Results: PPR blocking ELISA based on the H-antigen demonstrated high-titres of PPRV-specific antibodies in all vaccinated animals regardless of vaccination route with peak mean percentage inhibitions of 79.3% (day 14); 69.8% (day 21) and 86.6% (day 21) for IN-Drop; IN-Spray and Subcutaneous vaccination groups, respectively. Pulmonary histomorphological assessment showed the development of bronchus-associated lymphoid tissues (BALT) in IN-Spray Group only. PPR Immunohistochemistry showed PPR viral antigens in the lymphoid cells of the germinal centers of the BALT. PPRV antigen was also detected in the spleen and mediastinal lymph nodes of all vaccinated animals after 28 days post-vaccination.
Discussion: The findings of this study shows that the choice of application methods for intranasal PPR vaccine delivery is essential in the induction of immune response and suggests that the IN-Spray method may hold greater potential for earlier induction of systemic immune response as well as pulmonary protection against the pneumonic form of the disease.