Protection from cytomegalovirus viremia following glycoprotein B vaccination is not dependent on neutralizing antibodies

Significance Conventionally, vaccines are screened for induction of a neutralizing antibody response in human volunteers before proceeding to late-stage clinical trials. We present results from a human cytomegalovirus (HCMV) challenge study suggesting that this paradigm may not apply universally to all viruses. Instead, viruses like HCMV, which establish lifelong infections and grow both cell-free and cell-associated, may be controlled independently of a potent neutralizing antibody response. Our results suggest that more detailed laboratory studies are required to identify correlates of immune protection for such viruses and that failure of a vaccine to induce a neutralizing antibody response should not necessarily be considered as a key go-no-go decision point in the design of future vaccine studies.