An influenza A virus (IAV) vaccine that provides better cross protection to pigs against heterologous strain infection and overrides maternal antibodies interference is desirable. A replicon particle (RP) platform has been developed for influenza vaccine for swine use by expressing influenza proteins.

Chapter 2 presented a review of influenza virus infection in swine, including a discussion of current vaccine approaches and techniques used for novel vaccine development.

The first animal study (Chapter 3), composing two experiments, demonstrated the efficacy of intranasal (IN) administration of RP expressing hemagglutin (HA) protein (HA RP) of Pandemic H1N1 (A/CA/04/2009) strain. Prime/boost HA RP vaccination was administered IN/IN to pigs, with IM/IM administration as positive control and sham vaccination as negative control (five pigs each group). All pigs were challenged by homologous challenge following two doses vaccination. Pigs were not protected by IN/IN administration of RP against IAV challenge. Virus titers and pneumonia were not reduced significantly in RP IN/IN administered group, compared with control group. In the second experiment, pigs were administered with one dose HA RP vaccine IM or IN, or with a combination of IN/IM routes with an interval of three weeks. At most, two pigs at 2 DPC and 3 DPC, and no pigs at 3 DPC to 5DPC in IN/IM or one dose IM administered pigs were isolated with live virus, while all five pigs were detected with live virus from one dose RP IN administered pigs and sham vaccinated pigs. We also found that one dose IM and combination of IN/IM vaccination with HA RP reduced pneumonia significantly compared with sham vaccinated group, contrary to one dose IN vaccination.

In the second animal study (Chapter 4), the immunogenicity of HA RPs of a H3N2 strain and a delta1 strain at varying doses [1×10⁷ (infectious unit) IU to 5×10⁵ IU], was evaluated. Two H3N2 RP vaccinated groups with 10⁶ IU or 5×10⁵ IU RP as negative control, and two delta1 RP vaccinated groups with 10⁶ IU or 5×10⁵ IU RP were all challenged with delta1 IAV virus homologous to delta1 RP. RPs at 5×10⁵ IU or higher doses tested in this study were sufficient to induce hemagglutinnin inhibition (HI) detectable antibodies. HI titers were greater at increasing vaccine doses. Delta1 RP 10⁶ IU or 5×10⁵ IU doses, which induced HI antibodies with mean titers equal to or lower than 20, partially prevent homologous infection by eliminating virus replication in lung at day 5 post challenge. However, compared with H3N2 RP vaccinated pigs, decreased lung lesions observed in delta1 RP vaccinated pigs were not statistically significant.