Vaccination time points are indicated by an arrow. Cells expressing CD154 (CD40L) represent a subset of CD4+ T cells that have recently been activated. end point dilution titer) and CD4+ T-cell responses in previously CMV-seropositive women by way of natural contamination. These data suggest that this vaccine is usually capable of improving immunity in a populace of CMV-infected women and warrants additional evaluation to determine whether these boosted responses may prevent mother to child transmission of CMV. Congenital cytomegalovirus (CMV) infections are a major public health problem in the United States. Preexisting immunity against CMV in the mother before conception has been shown to provide substantial protection against congenital CMV contamination PEG6-(CH2CO2H)2 in the newborn [1]. However, women who are seropositive for CMV whose CMV contamination is usually reactivated [2] or who are reinfected with a different strain of CMV can sometimes transmit the computer virus during pregnancy, resulting in symptomatic congenital contamination [3]. The ability of the immune system to mount an PEG6-(CH2CO2H)2 effective and protecting secondary response that will survive long term after an encounter with a pathogen is the cornerstone of immunological memory and the basis for the development of vaccines [4]. Thus, the availability of a CMV vaccine capable of improving immunity in a previously immune populace of individuals may aid in the prevention of mother-to-child transmission of CMV. Although there are scant data in vaccination regimens for immune populations, CD4+ T-cellmediated immunity has been implicated in the prevention of herpes zoster, and the improving of varicella zoster virusspecific PEG6-(CH2CO2H)2 immunity was exhibited with the recently developed zoster vaccine [5]. A study attempting to understand the correlates of immune protection during the main immune response to PEG6-(CH2CO2H)2 CMV decided that the formation of effector memory CD4+ T cells was necessary for recovery of contamination [6]. Recently, a CMV glycoprotein B (gB) vaccine with MF59 administered to CMV-seronegative women was shown to prevent contamination in women of childbearing age [7]. In these studies, we set out to analyze both the antibody and the CD4+ T-cell response after gB/MF59 vaccination in women with preexisting immunity to CMV. == MATERIALS AND METHODS == == Study Population == The study enrolled women 1440 years of age (median age for both vaccine and placebo groups, 26 years) who screened seropositive for CMV, using a commercial CMV immunoglobulin (Ig) G assay (Axsym CMV IgG; Abbott) as previously explained [1]. A total of 150 women were enrolled in the study (120 received the vaccine and 30 received placebo). The 4:1 vaccine: placebo ratio allowed for additional power to detect safety, as is usually standard for phase I studies. To perform the CD4+T-cell studies, the first 40 women were enrolled in this substudy; 32 women were vaccinated intramuscularly (IM), and 8 received placebo. In both the vaccine and placebo groups, 75% of the women enrolled were African American, and the remaining women were Caucasian. Informed consent was obtained from all subjects under the guidelines of the US Department of Health and Human services and the Institutional Review Table of the University of Alabama at Birmingham (UAB). == Vaccination and Blood Specimen Collection == The CMV vaccine (gB/MF59) [7] was composed of 20 g of gB and MF59 (squalene, sorbitan trioleate, and polysorbate 80 with citrate buffer) in 0.5 mL of buffered saline. The placebo was saline. Vaccinations were administered IM on day 0, at 1 month, and at 6 months. Blood specimens were collected at day 0 (prevaccination), day 14 (2 weeks after the first vaccination), day 180, day 194 (2 weeks after the third vaccination) and day 360 for T-cell assays. Serum specimens were collected at day Rabbit Polyclonal to FCGR2A 0 (prevaccination), day 28 (4 weeks after first vaccination), day 180 (prior to third vaccination), day 208 (4 weeks after third vaccination), and day 360 for antibody measurements (Determine 1). Peripheral blood mononuclear cells (PBMCs) were isolated by standard Histopaque (Sigma-Aldrich) density centrifugation and were cryopreserved as previously explained [8]. The data analysis was carried out in a blinded fashion, with the code revealed only after the assays were PEG6-(CH2CO2H)2 completed. == Determine 1. == Immunization routine..
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