Live attenuated vaccines alone or in combination with an adenovirus-based vaccine protect mice lacking IFN-γ against pneumonic plague.

Abstract

Two live-attenuated vaccines, LMA and LMP, were evaluated alone or in combination with a trivalent adenoviral vector-based vaccine (Ad5-YFV) for their protective efficacy against pneumonic plague in wild-type (WT) and interferon-γ (IFN-γ) knockout (KO) mice. LMA and LMP comprise triple deletion mutants of <i>Yersinia pestis</i> CO92, which causes pneumonic plague, and Ad5-YFV incorporates three protective plague immunogens. Protection of 80 to 100% was observed in vaccinated mice when challenged with highly lethal intranasal doses of parental <i>Y. pestis</i> CO92. All vaccinated mice generated robust humoral and cellular immune responses. Immunized WT mice generated overall greater antibody responses in both serum and bronchoalveolar lavage fluid with higher percentages of polyfunctional T cell populations. Vaccinated IFN-γ KO mice displayed better B cell activity in germinal centers with higher percentages of activated antigen-specific and memory T cells. Superior lung immunity and recall immune responses were observed in both WT and IFN-γ KO mice immunized using a prime-pull vaccine strategy, which also provided full protection against pneumonic plague to mice lacking IFN-α, IFN-β, and IFN-γ receptors. Depletion of IFN-γ or tumor necrosis factor-α from immunized WT mice before and during infection did not reduce protection against pulmonary <i>Y. pestis</i> CO92 challenge. These data suggest that IFN-γ may not be required for protection against pneumonic plague by these vaccines. Combining live-attenuated and adenovirus-based vaccines resulted in augmentation of systemic and local immune responses, which could be beneficial in providing long-lasting immunity against pneumonic plague.