Morphometry, cellular characterization and temporal evolution of granulomas induced by aluminium oxyhydroxide in sheep

Persistent subcutaneous granulomas form at the injection site following administration of aluminium oxyhydroxide (AlOOH), a widely used vaccine adjuvant. Small ruminant lentiviruses (SRLVs) can infect macrophages within granulomas induced by commercial AlOOH-based vaccines in sheep. The entry of SRLVs into target cells involves the mannose receptor (MR), while catalytic polypeptide-like 3 protein containing Z1 domain (A3Z1) is considered a restriction factor for lentiviral replication. The objective of this study was to investigate the temporal evolution of AlOOH-induced post-vaccination granulomas in sheep experimentally infected with SRLVs. Twenty-four male lambs underwent two identical vaccination protocols and were challenged with SRLVs. Granulomas were detected in vaccinated groups only and progressively decreased in size. At post-mortem examination, 91.3% of the granulomas were recovered. Fistulas were present in granulomas following the second vaccination protocol. Central necrosis was present in 58.0% of granulomas and was associated with the vaccine used. Orthokeratotic keratin was seen within granulomas in 47.1% of the lambs. Considering all granulomas studied, significantly higher expression of MR was found compared with A3Z1. Differences in MR expression were related to the type of vaccine and the time since vaccination. A3Z1 expression was upregulated in granulomas from the infected groups. Macrophage polarization may influence SRLV infection of granulomas. While SRLV infection does not influence the architecture of post-vaccination granulomas, it may modulate their immune microenvironment. Further studies are needed to elucidate the complex interactions between AlOOH-induced granulomas and SRLV infection in sheep.

This study was supported by the Spanish Ministry of Science, lnnovation and Universities (RTl2018-096172-B-C33) and the Recognized Research Group of the Government of Aragón (A17_17R, Animal Health and Reproduction). A. Rodríguez-Largo was a PhD student funded by the Spanish Ministry of Science, Innovation and Universities (grant reference: FPU18/01674).

Peer reviewed