Respiratory mucosal immunization with adenovirus gene transfer vector induces helper CD4 T cell‐independent protective immunity

Abstract

Virus-vectored vaccine is a powerful activator of CD8 T cell-mediated immunity and is especially amenable to respiratory mucosal immunization, offering hopes for use in humans with diminished helper CD4 T cell function. However, whether virus-mediated mucosal immunization can produce immune protective CD8 T cells without the CD4 T cell help remains to be investigated. We used a replication-deficient adenovirus vector expressing an Mycobacterium tuberculosis antigen Ag85A for intranasal vaccination and evaluated its effect on CD8 T cell activation and protection in mice depleted of CD4 T cells. Intranasal vaccination of CD4 T cell-depleted mice led to suboptimal generation of Ag-specific tetramer(+) or interferon (IFN)-gamma-producing CD8 T cells in the lung and spleen but this was observed mainly at the early time after vaccination. Reduced CD8 T cell priming was also accompanied by decreased CD8 T cell responses (CTL). Nevertheless, the ratio of Ag-specific CD8 T cells to IFN-gamma-producing CD8 T cells in CD4 T cell-depleted hosts remained comparable to that in CD4 T cell-competent hosts. Furthermore, the 'unhelped' CD8 T cells also displayed a similar immune phenotype as the 'helped' counterparts. The animals with 'unhelped' CD8 T cells were as well-protected from pulmonary M. tuberculosis challenge as those with 'helped' CD8 T cells in the absence of CD4 T cells. The data obtained in the present study suggest that the fully immune protective CD8 T cells can still be generated by respiratory mucosal viral-mediated immunization without CD4 T cells and that CD8 T cells, 'helped' or 'unhelped', can confer significant protection against pulmonary tuberculosis independent of CD4 T cells.