Dynamics of adaptive natural killer cells in longitudinal analysis of CMV vaccine recipients

Abstract

Abstract While cytomegalovirus (CMV) infection poses a considerable burden to public health, an efficacious vaccine is not yet available. Classical vaccine efforts focusing on the induction of B- and T-cell memory have proven ineffective and, therefore, CMV remains a significant public health threat. The incidence of recurrent, severe infections with cytomegalovirus (CMV) and other DNA viruses in patients lacking functional natural killer (NK) cells highlight the importance of these cells in viral control. Therefore, the marked expansion of phenotypically and functionally distinct subsets of NK cells during CMV infection may represent a component of immune control of CMV that should be replicated in vaccines. We interrogated blood leukocytes samples collected longitudinally during a CMV glycoprotein B vaccine trial to ascertain induction or accumulation of these unique CMV-associated subsets of NK cells. We observe tantalizing expansions of CMV-associated subsets of NK cells in some CMV-negative vaccine recipients, that are unexpectedly mirrored by similar expansions in placebo-recipients. Moreover, these subpopulations exhibit marked contractions or patterns of alternating expansion and contraction in other trial participants. Importantly, this unique longitudinal data in healthy CMV-seronegative individuals indicates that NK-cell subsets may react to unknown environmental or inflammatory cues and demonstrate greater flux that appreciated from past cross-sectional studies.