To determine the safety, immunogenicity, and efficacy of a recombinant herpes simplex virus type 2 glycoprotein D and B vaccine in the treatment of recurrent genital herpes, a randomized, placebo-controlled trial was held at two referral centers. Healthy patients with 4-14 recurrences per year received injections of both glycoproteins in MF59 adjuvant or of MF59 alone at 0, 2, 12, and 14 months. For 18 study months, the rate and number of recurrences, the duration and severity of the first confirmed recurrence, vaccine immunogenicity, and rates of local and systemic reactions were determined. The monthly rate of recurrences was not significantly improved, but the duration and severity of the first study outbreak was reduced significantly by vaccination. Glycoprotein-specific and neutralizing antibodies were boosted by vaccination for the duration of the study. This vaccine is safe and immunogenic and ameliorated an observed first postvaccination genital recurrence, but it does not reduce recurrence frequency.

In our study of adults with CFS, fludrocortisone as monotherapy for NMH was no more efficacious than placebo for amelioration of symptoms. Failure to identify symptomatic improvement with fludrocortisone does not disprove the hypothesis that NMH could be contributing to some of the symptoms of CFS. Further studies are needed to determine whether other medications or combination therapy are more effective in treating orthostatic intolerance in patients with CFS.

The clinical spectrum of herpes simplex virus (HSV) infections, ranging from asymptomatic to frequently distressing outbreaks, suggests that there may be immunologic determinants of disease severity that are associated with human leukocyte antigen (HLA) expression. A controlled, prospective study identified several major histocompatibility complex (MHC) class I and II antigens whose frequencies are associated with HSV-2 infection or with frequent symptomatic genital recurrences. Previous studies were hampered by the inability to serologically identify patients with asymptomatic HSV-2 infection. Clinical evaluation and Western blot assay were used to identify 3 subject cohorts: 1 with no prior HSV infections, 1 with HSV-2 antibodies but no recognized symptoms, and 1 with HSV-2 antibodies and frequent genital recurrences. Statistical comparisons of HLA frequencies among these cohorts showed associations of HLA-B27 and -Cw2 with symptomatic disease. Also, HLA-Cw4 was significantly associated with HSV-2 infection. These associations indicate that immunologic factors linked to the MHC influence the risk of HSV-2 infection and disease expression.

Epstein-Barr virus (EBV) establishes a latent infection in B cells in the bloodPrimary infection with Epstein-Barr virus (EBV) is frequently asymptomatic in infants and children, but infection of adolescents and young adults can result in infectious mononucleosis. EBV is associated with several malignancies, including Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, and lymphoproliferative disease, in immunocompromised and immunocompetent persons (6,20).In healthy EBV-seropositive persons, about 1 to 10 in 10 5 peripheral B cells are infected with EBV (14). The virus establishes latency in memory B cells. The level of the latent EBV load in healthy individuals remains stable over time, maintaining a "set point" for each individual (19). It is uncertain how this "set point" is maintained, but the latent EBV load is thought to reflect a balance between removal of EBVinfected cells due to the half-life of memory B cells and reinfection of new memory B cells during virus reactivation. The EBV genome replicates when B cells latently infected with EBV divide using the host DNA polymerase, which is not sensitive to the action of acyclovir. However, when the virus reactivates in latently infected B cells, EBV replicates using the viral DNA polymerase, which is inhibited by the phosphorylated form of acyclovir. Therefore, blocking production of new virus with acyclovir should decrease the latent EBV load at a rate equivalent to the half-life of memory B cells. Patients with zoster who were treated with oral acyclovir for 28 days showed no reduction in the EBV load in the blood, despite complete inhibition of EBV shedding in the saliva (23). These results suggested that antiviral therapy for longer than 28 days is necessary to detect a reduction in the EBV load in the blood. In this study, we administered either valacyclovir (valaciclovir) (which is absorbed more effectively than acyclovir and metabolized to acyclovir) or no antiviral to healthy volunteers for 12 months and measured the level of EBV DNA in the blood every 3 months. MATERIALS AND METHODS Subjects.Patients at the National Institutes of Health Clinical Center and at the University of Texas Center for Clinical Studies with a history of recurrent genital herpes with three to nine recurrences a year and either a positive culture for herpes simplex virus (HSV) from the genital area or a positive serology for HSV type 2 (HSV-2) received valacyclovir at 500 mg per day for 1 year. Patients with genital herpes were required to be off HSV-suppressive therapy for 3 months before entering the study. The control group did not have symptomatic genital herpes and received no antiviral therapy. Subjects were excluded if they were receiving immunosuppressive therapy, had malignancy, or were infected with human immunodeficiency virus. Informed consent was obtained from all subjects, and the study was approved by the institutional review boards of the National Institute of Allergy and Infectious Diseases and the University of Texas Center for Clinical Studies....

Background The smallpox vaccine has more serious side effects associated with it than other live attenuated vaccines in use today. While studies have examined serum cytokines in primary vaccinees at 1 and 3-5 weeks after vaccination with the smallpox vaccine, serial measurements have not been performed nor have studies been performed in revaccinees. Methods We analyzed cytokine responses every other day for two weeks after vaccination in both primary vaccinees and revaccinees. Results Primary vaccinees had maximal levels of G-CSF on days 6-7 after vaccination, peak levels of TNF-α, sTNFR1, IFN-γ, IP-10, IL-6, and TIMP-1 on days 8 to 9 after vaccination, peak levels of sTNFR-2 and MIG on days 10 to 11 after vaccination, and peak levels of GM-CSF at days 12-13 after vaccination. Primary vaccinees were significantly more likely to have higher peak levels of IFN-γ, IP-10, and MIG after vaccination than revaccinees. Primary vaccinees were significantly more likely to have fatigue, lymphadenopathy, and headache compared with revaccinees and a longer duration of these symptoms as well as missed hours from work than revaccinees. Conclusions The increased symptoms observed in primary vaccinees compared with revaccinees paralleled the increases in serum cytokines in these individuals.

The authors of a recent study suggested that the duration of deferral for blood donations by smallpox vaccinees should be extended, based on detection of vaccinia virus DNA in 5 blood samples by PCR and the potential for viremia. We found that 4 of 202 blood specimens (from 3 of 27 smallpox vaccinees) were positive for vaccinia virus DNA by PCR; none were positive for virus by culture. Throat swabs were negative by PCR and culture. Thus, while some blood specimens contained vaccinia virus DNA, infectious virus was not detected. Current guidelines for deferral of blood donation in vaccinees seem appropriate.

We analyzed a shell vial culture assay (SVA), real-time PCR, and a direct fluorescent antibody assay (DFA) for rapid detection of vaccinia virus from vaccination sites of Dryvax vaccine recipients. Of 47 samples assayed, 100% were positive by PCR, 89% were positive by SVA, and 40% were positive by DFA. DFA was limited by the need for adequate numbers of cells, with 32% of samples inadequate for interpretation. DFA performed better with specimens from patients who had not previously received the vaccine. PCR was positive for longer times postvaccination than was SVA. Infectious virus could be recovered after 45 min of acetone fixation of shell vial coverslips. Commercially available polyclonal antibodies cross-reacted with other orthopoxviruses and herpes simplex 1, but commercially available monoclonal antibodies were specific for vaccinia virus. In summary, PCR was the most sensitive test for detecting vaccinia virus in clinical specimens, while the DFA was the most rapid but the least sensitive test.

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