Porcine circovirus type 2 (PCV2) is the primary pathogen of porcine circovirus diseases and porcine circovirus associated diseases. Immunization with a
vaccine is considered an effective measure to control these diseases. However, it is still unknown whether PCV2
vaccines have protective immune responses on the animals infected with
swine influenza virus (SIV), a pandemic virus in swine herds. In this study, we first compared the effects of 2 different PCV2
vaccines on normal mice and SIV-infected mice, respectively. The results showed that these two
vaccines had protective immune responses in normal mice, and the
subunit vaccine (
vaccine S) had better effects. However, the
inactivated vaccine (
vaccine I) instead of
vaccine S exhibited more immune responses in the SIV-infected mice. SIV
infection significantly decreased the immune responses of
vaccine S in varying aspects including decreased PCV2 antibody levels and increased PCV2 replication. Mechanistically, further studies showed that SIV
infection increased
IL-10 expression and M2 macrophage percentage, but decreased TNF-α expression and M1 macrophage percentage in the mice immunized with
vaccine S; on the contrary, macrophage depleting by using
clodronate-containing
liposomes significantly alleviated the SIV
infection-induced decrease in the protective immune responses of
vaccine S against PCV2. This study indicates that SIV
infection decreases the protective immune responses of
vaccine S against PCV2. The macrophage polarization induced by SIV
infection might facilitate decreased immune responses to
vaccine S, which provides new insight into
vaccine evaluation and a reference for the analysis of immunization failure.