A Randomized Dose-Escalating Phase I Trial of a Replication-Deficient Lymphocytic Choriomeningitis Virus Vector-Based Vaccine Against Human Cytomegalovirus.

Background: A vaccine (HB-101) consisting of 2 nonreplicating lymphocytic choriomeningitis virus (LCMV) vectors expressing the human cytomegalovirus antigens glycoprotein B (gB) and the 65-kD phosphoprotein (pp65), respectively, is in development to prevent cytomegalovirus infection.

Methods: HB-101 was tested in cytomegalovirus-naive, healthy adults in a randomized, double-blind, placebo-controlled, dose-escalation Phase I trial. Fifty-four subjects received low, medium, or high dose of HB-101 or placebo by intramuscular administration at Month 0, 1, and 3.

Functional Exhaustion Limits CD4+ and CD8+ T-Cell Responses to Congenital Cytomegalovirus Infection.

Background: Cytomegalovirus (CMV) infection during fetal life causes severe symptoms and is associated with prolonged viral excretion. Previous studies reported low CD4(+) T-cell responses to CMV infection in early life, contrasting with large responses of effector CD8(+) T cells. The mechanisms underlying the defective CD4(+) T-cell responses and the possible dissociation with CD8(+) T-cell responses have not been clarified.

Immunity to cytomegalovirus in early life.

Cytomegalovirus (CMV) is the most common congenital infection and is the leading non-genetic cause of neurological defects. CMV infection in early life is also associated with intense and prolonged viral excretion, indicating limited control of viral replication. This review summarizes our current understanding of the innate and adaptive immune responses to CMV infection during fetal life and infancy.

Functional exhaustion of CD4+ T lymphocytes during primary cytomegalovirus infection.

Human CMV establishes lifelong persistence after primary infection. Chronic CMV infection is associated with intermittent viral reactivation inducing high frequencies of CD4+ T lymphocytes with potent antiviral and helper properties. Primary CMV infection is characterized by an intense viral replication lasting for several months.