NK-CTL induction by RhCMV-based vaccines

Award amount: 50,000.00

Rhesus CMV-vectored SIV (RhCMV/SIV) vaccines have been shown to protect half of vaccinated adult macaques against progressive infection. The vectors elicit unconventional Mamu class II- or Mamu E-restricted CD8+ T cells. The viral backbone of RhCMV/SIV vaccines, cytomegalovirus (CMV), is known to have a panoply of immunologic effects including generation of effector-memory CTLs and “memory” NK cells—innate cells with adaptive features. It has also been proposed that CMV infection can elicit adaptive immune cells with innate features, e.g., NK-CTLs, which are TCRαβ+, HLA-E-restricted CTLs with a ‘NK-like’ activity.

I recently conducted the first study of RhCMV/SIV vaccines administered to infant macaques. The results show that infants readily generate responses to the vaccine insert (SIV gag). The responses include CTLs that are specific for known Mamu-E-restricted peptides and inhibited by Mamu-E-specific inhibitors. In addition, however, I found that many vaccinated or wild-type RhCMV-infected infants generated substantial populations of TCRαβ+ cells expressing inhibitory NK cell receptors—a phenotype suggestive of NK-CTLs. In the next phase of my research I wish to test the contribution of these cells to protection of infants against oral challenge with SIV.