Dodging NK Cells May Produce More Robust Vaccines Against HIV

Published September 25, 2018 | Cell Reports

When vaccines succeed, they prompt the immune system to form germinal centers (GC) that act like factories to pump out hordes of high-affinity B cells equipped to attack invading pathogens. But sometimes the factories fail to produce more than a trickle.

Now researchers at Cincinnati Children’s, in collaboration with colleagues at Yale University, have discovered one of the key reasons why: a discovery that has deep implications for developing more effective vaccines against HIV.

Natural killer (NK) cells are a vital defense against invading viruses. However, new research shows that NK cells also kill some of the helper T cells needed for GC formation. These weakened factories fail to produce the wide variety of antibodies needed to mount a robust defense against fast-mutating invaders like HIV.

The study was led by senior author Stephen Waggoner, PhD, and first author Carolyn Rydyznski, PhD. Cincinnati Children’s co-authors included Stacey Cranert, PhD, Heping Xu, PhD, and Harinder Singh, PhD (now at the University of Pittsburgh).

“Circumventing this activity of NK cells during vaccination has strong potential to enhance humoral immunity and facilitate vaccine-elicited prevention of disease,” Waggoner says.

The team traced the NK cells’ ability to suppress affinity maturation to a mechanism involving perforin, a molecule that forms pores in membranes to help trigger cell death. When the team used lines of mice that produced less perforin, test vaccines prompted larger numbers of helper T cells and high-affinity B cells in response.

“Our results highlight the potential for interventions that limit NK cell suppression of GC reactions as a strategy to potentiate vaccine-induced, GC-mediated generation of heavily mutated high-affinity antibodies capable of broad neutralization of HIV infection,” the co-authors say.