Injection of aluminum (Al) adjuvants induces formation of long-lasting granulomas, composed of activated macrophages. These granulomas have a key role in the development of the ovine ASIA syndrome and may represent a threat in macrophage-tropic viral infections. Small Ruminant lentiviruses (SRLV) are retroviruses that infect and actively replicate in macrophages. The aim of this work is to evaluate the interaction between Al-containing postvaccination granulomas and SRLV.
Eleven adult ewes affected by lentiviral disease were inoculated with 8 doses of: i) Commercial Al-based vaccines (Vaccine group; n=6); ii) Alhydrogel® (Adjuvant-only group; n=3); iii) PBS (Control group; n=2). SRLV-antibodies and viral load were measured at the beginning and the end of the experiment by ELISA and qPCR, respectively. DNA from peripheral blood mononuclear cells (PBMCs), Al-containing granulomas and other tissue samples was obtained. LTR, pol and env regions were amplified and sequenced. Immunohistochemistry of infected granulomas was performed against SRLV.
Granuloma formation was constant in Vaccine and Adjuvant-only groups. Presence of SRLV in granulomas reached about 50% of samples analyzed. Viral protein was localized within macrophages in granulomas. In three sheep, the viral strain found in the granuloma was different from strains isolated in PBMC or other tissues in the same animal and recombination was appreciated.
Al-induced granulomas provide suitable ground for SRLV replication and favor the generation of new viral strains. This interaction between a secondary vaccine reaction and a retrovirus is shown here for the first time in and opens an unexplored avenue in other mammal species, including humans.