Field evaluation of novel livestock vaccines

28 Mar 2019

On 1 November 2018 thirty delegates assembled for the IVVN workshop on “Field evaluation of novel livestock vaccines” organised by Nick Lyons (EuFMD – FAO, Italy/Pirbright Institute, UK) and Eyal Klement (Associate Professor of Veterinary Epidemiology, Koret School of Veterinary Medicine, Hebrew University, Israel). The workshop followed the EuFMD Open Session on the subject of Global Vaccine Security.

 

The workshop explored the importance of field trials through twelve talks covering the principles of trial design, regulatory requirements, successes and challenges of specific case studies. The workshop comprised three sessions: Background and experience with vaccine evaluation in the field; Planning for field trials; and Vaccines under development. In the welcome and introductions, Eyal Klement stated the value of field trials as the best, most cost-efficient, effective and reliable way to test the efficacy and efficiency of vaccines. Nick Lyons and Eyal Klement also highlighted the lack of research funding for field trials, and the significant opportunity for academic, development and industry to expand field trial operations.

Paul Fine, Professor of Communicable Disease Epidemiology at the London School of Hygiene and Tropical Medicine (UK) opened the first session with a talk on “Principles of trial design for determining field efficacy of novel vaccines.” Paul outlined the purpose of field trials: “To evaluate the efficacy/effectiveness of a vaccine in preventing disease correctly and convincingly”. He covered and defined terminology, development pipelines, study phases, and compared challenge studies and field trials.

Frida Hasslung Wikstrom, senior clinical assessor at the department of licensing for the Swedish Medical Products Agency (Sweden), presented her personal views on the “Regulatory requirements for animal vaccines”. She outlined the legal framework for immunological veterinary medicinal products in Europe, particularly Directive 2001/82 EC as amended, European Pharmacopoeia, scientific and regulatory guidance from the committees of EMA (European Medicines Agency), and the complexities of European and member state regulations and legislation. Frida spoke about the need for data, specifically field data and field efficacy and field safety data when developing drugs for market authorisation.

Claude Hamers, Technical Director of the Veterinary Public Health Center of Boehringer Ingelheim Animal Health, gave an industry perspective on field trials in “Field trials for novel animal vaccines – experience from industry”. Claude focussed on assessment of the safety of vaccines and assessment of the efficacy of vaccines. He discussed costs, challenges (such as herd selection, intercurrent diseases and data collection), and the realities of highly variable conditions in field trials. He underscored the talk with three examples of vaccine trials involving pregnant cows, swine and calves. Claude concluded, “Analyze results considering the effects of each variable, … including some variables that you were not initially expecting” and highlighted the imperative of traceability.

Eyal Klement talked on “Testing the efficacy of lumpy skin disease vaccines in the field”. He gave an overview of lumpy skin disease (LSD) including clinical signs and global geographical distribution. Eyal then focussed on a LSD outbreak in Israel 2012-13, and discerning a good vaccine – one that is safe and efficacious – through the comparison of two LSD vaccines.

Annie Cook, a veterinary epidemiologist at ILRI in Kenya, gave a presentation via skype on “A vaccine trial in Kenya demonstrated protection against wildebeest-associated malignant catarrhal fever in cattle”. Annie laid out the background of MCF, MCF vaccines and the study site, before discussing the field trial. She concluded by raising the importance of market scoping, safety and risk mapping.

Michael van Straten, head of the Department of Herd Health and Epidemiology at Hachaklait Veterinary Services (Israel), provided a presentation entitled “Brucella abortus S19 vaccine protects dairy cattle against natural infection with Brucella melitensis”. Michael began by discussing some of the challenges of field trials, such as ethics, expense, and lack of facilities. He moved on to compare randomized, controlled (blinded) trials vs. real life, and the effect of bias. Michael’s talk focussed on an outbreak of Brucella melitensis in Israel in October 2015 following the end of compulsory vaccination with Brucella abortus S19 vaccine, “possibly the only evidence for cross protection B. melitensis with B. abortus strain in dairy cattle”. He highlighted the monitoring, baselining and coordination of regulations and policies in Israel that created conditions for a natural experiment on vaccine effectiveness. He concluded that the “Findings have influenced decisions regarding use of S19 in dairy farms.”

Madeleine Clark, PhD student at Pirbright Institute (UK) opened the second session with a talk on “A field trial assessing the immunogenicity of a novel Rift Valley Fever vaccine in multiple species in Kenya: planning, challenges and collaborations – learning on the ground”. Madeleine described her work on a novel RVF vaccine using a Chimpanzee Adenovirus Vector, and a non-inferiority immunogenicity field trial at ILRI.

Georgina Limon-Vega, a veterinary epidemiologist at Pirbright Institute (UK), gave a talk on an “Efficacy study for a novel vaccine against Crimean-Congo haemorrhagic fever (CCHF) in Bulgaria”. The purpose of the project was to assess the efficacy of vaccine in sheep and the objective of the trial was to “assess whether the vaccine prevents infection in sheep (to limit exposure of humans) after natural challenge in a field study in an endemic area, during periods of high levels of transmission in the tick season.” Georgina talked about the importance of working with local communities and farmers as partners in field trials, in particular that it is “very helpful to discuss unexpected results with field vets”.

The third session opened with a presentation over skype by Shintuou Cabirou Mounchili, PhD student at the University of Buea (Cameroon). Shintouo talked about “Design of a multi-antigenic, multi-stage and multi-epitope vaccine candidate against onchocerciasis and related filarial diseases”. He talked about the social and economic burdens of onchocerciasis – approximately 15.5 million worldwide are infected – and the mitigation strategies. He outlined his work on a novel vaccine Ov-DKR, and concluded it “demonstrates superior antigenicity to the current individual lead vaccine candidates”, and that “Ov-DKR could act as a therapeutic and prophylactic vaccine.”

Chukwunonso Ezeasor, PhD Student at the University of Nigeria, gave a presentation by skype on “Comparative evaluation of the mucoadhesive strengths of Abelmoschus esculentus and Irvingia gabonensis gums for possible applications in veterinary mucoadhesive vaccine delivery systems.” He began with “Studies have shown that mucosal vaccination can successfully induce both systemic and mucosal immune responses, thus preventing the invasion and colonization of pathogens on the mucosal surfaces.” Chukwunonso concluded, “I. gabonesis (bush mango) gum is more suitably for use in mucoadhesive delivery in ruminants more than A. esculentus (okra) gum…The findings of this work have also shown that the methods of polymer extraction, plays a very important role in the mucoadhesiveness.”

Moez Mhadhbi, Assistant Professor in Veterinary Parasitology at the Veterinary School of Sifi Thabet (Tunisia), talked on the subject of “Development of a new live attenuated vaccine system for tropical theileriosis [TT] – The way forward for improving the control of tropical theileriosis in Tunisia”. He outlined the symptoms of TT and the Theileria annulata life cycle. He highlighted the scale of the problem – “400 million cattle are threatened throughout a large geographic area, possible extension to other regions with Climate Change.” – and the economic cost. Moez discussed many considerations in vaccine development and design, including the demographic and seasonal aspects of TT in Tunisia, farm typology and cattle population dynamics. He also raised the important issue of the size of the final product and thermostability, “vaccine bottles volume to be adapted to the average size of farms to avoid waist of vaccine particularly if frozen”.

Adeyinka Adedeji, Principal Veterinary Research Officer in the Viral Division of the National Veterinary Research Institute (Nigeria) gave the final talk on “Development of love attenuated goat pox vaccine in Nigeria”. Adeyinka outlined goat pox and sheep pox, and the costs and implications of goat pox – “GTP causes considerable economic losses due to morbidity, mortality, depreciation of wool and skin quality and international trade restrictions…outbreaks are frequently reported with mortality up to 49%-64.4%”. He concluded that the GTP vaccine developed at NVRI “has the potential to protect against both SPP and GTP although no field trial has been carried out.”

After the final talk, delegates engaged in a spirited discussion of the presentations, challenges and opportunities related to field trials, regulatory frameworks, licensing, commercialisation, distribution and implementation of vaccination programmes, and funding. The workshop concluded with a reiteration of the value of field trials as the best, most cost-efficient, effective and reliable way to test the efficacy and efficiency of vaccines. The other primary conclusion was the lack of funding for field trials, and the significant opportunity for academic, development and industry to expand field trial operations.

Thank you very much to all excellent speakers for thought-provoking presentations. Thank you to the delegates for attending the workshop and engaging in discussions and forging new collaborations. Thank you to the EuFMD team for organising the workshop.

All presentations from the workshop are available: https://www.eufmd.info/workshops.

For more information please contact Nick Lyons (nicholas [dot] lyons [at] fao [dot] org; nicholas [dot] lyons [at] pirbright [dot] ac [dot] uk) or Eyal Klement (eyal [dot] klement [at] gmail [dot] com).