Taking a Promising Vaccine Candidate Further: Efficacy of ASFV-G-ΔMGF after Intramuscular Vaccination of Domestic Pigs and Oral Vaccination of Wild Boar

Deutschmann, Paul; Carrau, Tessa; Sehl-Ewert, Julia; Forth, Jan Hendrik; Viaplana, Elisenda; Mancera, Jose Carlos; Urniza, Alicia; Beer, Martin; Blome, Sandra

doi:10.3390/pathogens11090996

Cited by 14 publications

(17 citation statements)

References 31 publications

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“…One of these mutations is silent (position 98378, A → G), the other leads to an amino acid exchange (position 98378, C → G; alanine → proline). In a previously published animal trial, no differences were observed in safety and efficacy 10 .…”

Section: Methodsmentioning

confidence: 75%

“…Considering this, undiluted master seed virus (MSV) was used and day 7 was set as timepoint for organ and blood collection for passaging. At this point, recovery of vaccine virus had the highest chance based on our experience from previous studies 10 . Along the same lines, an intramuscular transfer of material was chosen to maximize the chance of infection given the experience that the parenteral route is much more efficient than an oral or oro-nasal inoculation (Guinat, Gogin et al 2016).…”

Section: Methodsmentioning

confidence: 88%

“…In the present study, we evaluated vaccine candidate “ASFV-G-∆MGF” 9 , 10 , from here on called “ΔMGF”), a genetically modified LAV that has shown a most promising efficacy profile, in a standard in vivo reversion to virulence study in naïve weaner pigs. In short, the vaccine virus was passaged five times in domestic pigs in accordance with VICH (International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products) guideline 41 for the examination of live veterinary vaccines in target animals for absence of reversion to virulence (reference number EMA/CVMP/VICH/1052/2004).…”

Section: Introductionmentioning

confidence: 99%

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Assessment of African swine fever vaccine candidate ASFV-G-∆MGF in a reversion to virulence study

et al. 2023

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African swine fever (ASF) has gained panzootic dimensions and commercial vaccines are still unavailable. Recently, a series of live attenuated vaccines has raised hope for an efficacious and safe vaccine, among them “ASFV-G-∆MGF”. We tested the latter in an in vivo reversion to virulence study in accordance with International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products guidelines. Upon forced animal passaging, a virus variant emerged that was associated with transient fever and an increased replication and shedding. However, all animals were healthy upon completion of the study and reversion to significant virulence was not observed. The genomic changes did not affect the recombination site but involved deletions and reorganizations in the terminal regions of the genome. Thus, our study underscores that in-depth safety characterization is needed for live ASF vaccines. For this particular candidate, additional studies should target long-term effects and transmission characteristics before thorough benefit-risk analysis can be carried out.

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Section: Methodsmentioning

confidence: 75%

Section: Methodsmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Assessment of African swine fever vaccine candidate ASFV-G-∆MGF in a reversion to virulence study

et al. 2023

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“…However, despite the absence of clinical signs, most of the pigs developed low levels of viremia. In a recent study when ten 6–8-week-old pigs were infected IM with ASFV-G-ΔMGF (1 × 10 3 or 1 × 10 4 HAD 50 ), none of the pigs developed ASF clinical signs other than fever in one of the animals on 12 dpi [ 50 ]. In both these experiments, the pigs were inoculated IM and therefore the IM route of inoculation was selected for our second experiment.…”

Section: Discussionmentioning

confidence: 99%

Characterization of an African Swine Fever Virus Field Isolate from Vietnam with Deletions in the Left Variable Multigene Family Region

Ambagala,

Goonewardene,

Kanoa

et al. 2024

Viruses

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In this paper, we report the characterization of a genetically modified live-attenuated African swine fever virus (ASFV) field strain isolated from Vietnam. The isolate, ASFV-GUS-Vietnam, belongs to p72 genotype II, has six multi-gene family (MGF) genes deleted, and an Escherichia coli GusA gene (GUS) inserted. When six 6–8-week-old pigs were inoculated with ASFV-GUS-Vietnam oro-nasally (2 × 105 TCID50/pig), they developed viremia, mild fever, lethargy, and inappetence, and shed the virus in their oral and nasal secretions and feces. One of the pigs developed severe clinical signs and was euthanized 12 days post-infection, while the remaining five pigs recovered. When ASFV-GUS-Vietnam was inoculated intramuscularly (2 × 103 TCID50/pig) into four 6-8 weeks old pigs, they also developed viremia, mild fever, lethargy, inappetence, and shed the virus in their oral and nasal secretions and feces. Two contact pigs housed together with the four intramuscularly inoculated pigs, started to develop fever, viremia, loss of appetite, and lethargy 12 days post-contact, confirming horizontal transmission of ASFV-GUS-Vietnam. One of the contact pigs died of ASF on day 23 post-contact, while the other one recovered. The pigs that survived the exposure to ASFV-GUS-Vietnam via the mucosal or parenteral route were fully protected against the highly virulent ASFV Georgia 2007/1 challenge. This study showed that ASFV-GUS-Vietnam field isolate is able to induce complete protection in the majority of the pigs against highly virulent homologous ASFV challenge, but has the potential for horizontal transmission, and can be fatal in some animals. This study highlights the need for proper monitoring and surveillance when ASFV live-attenuated virus-based vaccines are used in the field for ASF control in endemic countries.

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“…The use of recombinant attenuated virus strains as potential vaccine candidates has recently increased [ 10 , 11 , 12 ]. Novel vaccine candidates were developed by deleting ASFV genes involved in the production of the disease in pigs.…”

Section: Introductionmentioning

confidence: 99%

Recombinant Vaccine Strain ASFV-G-Δ9GL/ΔUK Produced in the IPKM Cell Line Is Genetically Stable and Efficacious in Inducing Protection in Pigs Challenged with the Virulent African Swine Fever Virus Field Isolate Georgia 2010

Ramirez-Medina,

Rai,

Espinoza

et al. 2024

Pathogens

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We have previously reported that the recombinant African Swine Fever (ASF) vaccine candidate ASFV-G-Δ9GL/ΔUK efficiently induces protection in domestic pigs challenged with the virulent strain Georgia 2010 (ASFV-G). As reported, ASFV-G-Δ9GL/ΔUK induces protection, while intramuscularly (IM), administered at doses of 104 HAD50 or higher, prevents ASF clinical disease in animals infected with the homologous ASFV g strain. Like other recombinant vaccine candidates obtained from ASFV field isolates, ASFV-G-Δ9GL/ΔUK stocks need to be produced in primary cultures of swine macrophages, which constitutes an important limitation in the production of large virus stocks at the industrial level. Here, we describe the development of ASFV-G-Δ9GL/ΔUK stocks using IPKM (Immortalized Porcine Kidney Macrophage) cells, which are derived from swine macrophages. We show that ten successive passages of ASFV-G-Δ9GL/ΔUK in IPKM cells induced small changes in the virus genome. The produced virus, ASFV-G-Δ9GL/ΔUKp10, presented a similar level of replication in swine macrophages cultures to that of the original ASFV-G-Δ9GL/ΔUK (ASFV-G-Δ9GL/ΔUKp0). The protective efficacy of ASFV-G-Δ9GL/ΔUKp10 was evaluated in pigs that were IM-inoculated with either 104 or 106 HAD50 of ASFV-G-Δ9GL/ΔUKp10. While animals inoculated with 104 HAD50 present a partial protection against the experimental infection with the virulent parental virus ASFV-G, those inoculated with 106 HAD50 were completely protected. Therefore, as was just recently reported for another ASF vaccine candidate, ASFV-G-ΔI177L, IPKM cells are an effective alternative to produce stocks for vaccine strains which only grow in swine macrophages.

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Taking a Promising Vaccine Candidate Further: Efficacy of ASFV-G-ΔMGF after Intramuscular Vaccination of Domestic Pigs and Oral Vaccination of Wild Boar

Cited by 14 publications

References 31 publications

Assessment of African swine fever vaccine candidate ASFV-G-∆MGF in a reversion to virulence study

Assessment of African swine fever vaccine candidate ASFV-G-∆MGF in a reversion to virulence study

Characterization of an African Swine Fever Virus Field Isolate from Vietnam with Deletions in the Left Variable Multigene Family Region

Recombinant Vaccine Strain ASFV-G-Δ9GL/ΔUK Produced in the IPKM Cell Line Is Genetically Stable and Efficacious in Inducing Protection in Pigs Challenged with the Virulent African Swine Fever Virus Field Isolate Georgia 2010

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