The Importance of Quality Control of LSDV Live Attenuated Vaccines for Its Safe Application in the Field

Abstract

Vaccination is an effective approach to prevent, control and eradicate diseases, including lumpy skin disease (LSD). One of the measures to address farmer hesitation to vaccinate is guaranteeing the quality of vaccine batches. The purpose of this study was to demonstrate the importance of a quality procedure via the evaluation of the LSD vaccine, Lumpivax (Kevevapi). The initial PCR screening revealed the presence of wild type LSD virus (LSDV) and goatpox virus (GTPV), in addition to vaccine LSDV. New phylogenetic PCRs were developed to characterize in detail the genomic content and a vaccination/challenge trial was conducted to evaluate the impact on efficacy and diagnostics. The characterization confirmed the presence of LSDV wild-, vaccine- and GTPV-like sequences in the vaccine vial and also in samples taken from the vaccinated animals. The analysis was also suggestive for the presence of GTPV-LSDV (vaccine/wild) recombinants. In addition, the LSDV status of some of the animal samples was greatly influenced by the differentiating real-PCR used and could result in misinterpretation. Although the vaccine was clinically protective, the viral genomic content of the vaccine (being it multiple Capripox viruses and/or recombinants) and the impact on the diagnostics casts serious doubts of its use in the field.

An in-depth bioinformatic analysis of the novel recombinant lumpy skin disease virus strains: from unique patterns to established lineage

“…Comparisons between the partial sequences obtained from the Kenyan/2011 isolate with LSDV/Russia/Saratov/2017 indicated that they were not identical, but similar to the five recombinant virus sequences analysed here a novel recombinant strain [ 34 ]. The parental sequences predicted to be involved in the generation of the novel recombinants observed in Kenya, Kazakhstan, Russia and China and Vietnam, are mirrored in the mixed composition recently described in the Lumpivax vaccine batch from Kevevapi, that was extensively used in Kazakhstan since 2016 [ 10 , 35 ]. Although there is no evidence to identify the time when, and if, the recombinants emerged in the vaccine batch at the manufacturer’s site, evidence of a 2016 batch of Lumpivax vaccine from Kevevapi already displayed both vaccine and field signatures, i.e.…”

“…Incorporation of new data in future studies will greatly improve our understanding of the global LSD epidemiology and capture important details of LSDV molecular evolution. The identification and analysis of all the novel recombinant strains, again reiterate the limitations of the current DIVA assays, the importance of next generation sequencing of circulating isolates as well as the quality inspections during vaccine productions [ 35 ].…”

Recombinant LSDV Strains in Asia: Vaccine Spillover or Natural Emergence?

“…As none of the other countries in the affected region used a homologous LSDV vaccine during the same period, it was suggested that the vaccine might have been responsible for the emergence of the recombinant strains [ 26 , 33 , 36 ]. In a previous study, Haegeman et al indeed obtained conflicting results when they analysed the Lumpivax vaccine with a series of PCR assays that allowed differentiation between infected and vaccinated animals (DIVA) [ 40 ]. Genetic characterisation using Sanger sequencing revealed the presence of Neethling-like, KSGP-like and GTPV-like sequences in the vaccine itself, as well as in samples taken from vaccinated animals.…”

“…Unfortunately, unlike other commercially available Neethling-based vaccines, not much is known about the Lumpivax vaccine. Although the vaccine is certified by the manufacturers KEVEVAPI (Nairobi, Kenya) and AU-PANVAC (Debre Zeit, Ethiopia) as containing the LSDV Neethling strain, a preliminary genetic characterisation by Haegeman et al [ 40 ] revealed the presence of both Neethling- and KSGP-like LSDV sequences. In addition, the authors also discovered typical GTPV sequences [ 40 ].…”

“…Although the vaccine is certified by the manufacturers KEVEVAPI (Nairobi, Kenya) and AU-PANVAC (Debre Zeit, Ethiopia) as containing the LSDV Neethling strain, a preliminary genetic characterisation by Haegeman et al [ 40 ] revealed the presence of both Neethling- and KSGP-like LSDV sequences. In addition, the authors also discovered typical GTPV sequences [ 40 ]. Even though these results raise serious concerns about the exact contents of the vaccine, it remains unclear whether the vaccine-like recombinant strains were already present in the vaccine or only emerged in the field.…”