High dose trivalent influenza vaccine compared to standard dose vaccine in patients with rheumatoid arthritis receiving TNF-alpha inhibitor therapy and healthy controls: Results of the DMID 10-0076 randomized clinical trial.

Introduction: Subjects with rheumatoid arthritis (RA) receiving tumor necrosis factor-inhibiting (TNFi) therapies are at risk for severe influenza, and may respond less well to influenza vaccine. We examined the safety and immunogenicity of high dose influenza vaccine (HD) compared to standard dose vaccine (SD) in participants with RA receiving stable TNFi.

Methods: A randomized, double-blinded, Phase II study was conducted in adults with RA receiving TNFi, and healthy, gender and age-matched control subjects.

Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine.

The cellular immune responses elicited by an investigational vaccine against an emergent variant of influenza (H3N2v) are not fully understood. Twenty-five subjects, enrolled in an investigational influenza A/H3N2v vaccine study, who received two doses of vaccine 21 days apart, were included in a sub-study of cellular immune responses. H3N2v-specific plasmablasts were determined by ELISpot 8 days after each vaccine dose and H3N2v specific CD4+ T cells were quantified by intracellular cytokine and CD154 (CD40 ligand) staining before vaccination, 8 and 21 days after each vaccine dose.

Safety and immunogenicity of investigational seasonal influenza hemagglutinin DNA vaccine followed by trivalent inactivated vaccine administered intradermally or intramuscularly in healthy adults: An open-label randomized phase 1 clinical trial.

Background: Seasonal influenza results in significant morbidity and mortality worldwide, but the currently licensed inactivated vaccines generally have low vaccine efficacies and could be improved. In this phase 1 clinical trial, we compared seasonal influenza vaccine regimens with different priming strategies, prime-boost intervals, and administration routes to determine the impact of these variables on the resulting antibody response.

Methods: Between August 17, 2012 and January 25, 2013, four sites enrolled healthy adults 18-70 years of age.

Safety and immunogenicity of unadjuvanted subvirion monovalent inactivated influenza H3N2 variant (H3N2v) vaccine in children and adolescents.

Objective: In response to the emergence of influenza viruses with pandemic potential, we evaluated a swine-origin influenza A/H3N2 variant (H3N2v) vaccine in children.

Study Design: This multicenter phase II open-label study assessed the safety and immunogenicity of two doses, 21 days apart, of investigational unadjuvanted subvirion monovalent inactivated H3N2v vaccine administered via intramuscular injection. Children 6-35 months of age received 7.

Correlation between herpes simplex virus neutralizing antibody titers determined by ELVIS cell and traditional plaque reduction assays.

Preventive viral vaccine efficacy trials require large-scale sample analysis to quantitate immune responses and their correlation with infection outcomes. Traditional plaque reduction assays measure a functionally important form of humoral immunity, neutralizing antibody titer. These assays, however, are time-consuming and laborious.

DNA vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age: A phase 1 randomized clinical trial.

Background: Children are susceptible to severe influenza infections and facilitate community transmission. One potential strategy to improve vaccine immunogenicity in children against seasonal influenza involves a trivalent hemagglutinin DNA prime-trivalent inactivated influenza vaccine (IIV3) boost regimen.

Methods: Sites enrolled adolescents, followed by younger children, to receive DNA prime (1 mg or 4 mg) intramuscularly by needle-free jet injector (Biojector), followed by split virus 2012/13 seasonal IIV3 boost by needle and syringe approximately 18 weeks later.

Cross-Reactive Antibody Responses to Novel H5Nx Influenza Viruses Following Homologous and Heterologous Prime-Boost Vaccination with a Prepandemic Stockpiled A(H5N1) Vaccine in Humans.

Recently, novel highly pathogenic avian influenza H5Nx viruses (clade 2.3.4.

Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial.

Background: Cytomegalovirus (CMV) is a leading cause of congenital infection and an important target for vaccine development.

Methods: CMV seronegative girls between 12 and 17 years of age received CMV glycoprotein B (gB) vaccine with MF59 or saline placebo at 0, 1 and 6 months. Blood and urine were collected throughout the study for evidence of CMV infection based on PCR and/or seroconversion to non-vaccine CMV antigens.

Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial.

Background: The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo).

Methods: In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18-65 years from the University of Maryland medical community and the Baltimore community.

Effect of Varying Doses of a Monovalent H7N9 Influenza Vaccine With and Without AS03 and MF59 Adjuvants on Immune Response: A Randomized Clinical Trial.

Importance: Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continue to occur. Hemagglutinin H7 administered alone is a poor immunogen necessitating evaluation of adjuvanted H7N9 vaccines.

Objective: To evaluate the immunogenicity and safety of an inactivated H7N9 vaccine with and without AS03 adjuvant, as well as mixed vaccine schedules that included sequential administration of AS03- and MF59-containing formulations and of adjuvanted and unadjuvanted formulations.

DNA priming for seasonal influenza vaccine: a phase 1b double-blind randomized clinical trial.

Background: The efficacy of current influenza vaccines is limited in vulnerable populations. DNA vaccines can be produced rapidly, and may offer a potential strategy to improve vaccine immunogenicity, indicated by studies with H5 influenza DNA vaccine prime followed by inactivated vaccine boost.

Methods: Four sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza DNA vaccine prime (n=65) or phosphate buffered saline (PBS) (n=66) administered intramuscularly with Biojector.

Safety and Immunogenicity of a Subvirion Monovalent Unadjuvanted Inactivated Influenza A(H3N2) Variant Vaccine in Healthy Persons ≥18 Years Old.

Background: Variant influenza A(H3N2) viruses (H3N2v) have transmitted recently from pigs to humans in the United States. Vaccines strategies are needed.

Methods: Healthy adults received 2 doses of subvirion H3N2v vaccine (15 µg of hemagglutinin/dose) 21 days apart in this open-label trial.

Immunogenicity of avian influenza A/Anhui/01/2005(H5N1) vaccine with MF59 adjuvant: a randomized clinical trial.

Importance: The need to respond quickly to potential influenza pandemics is important. Immunologic priming (initial presentation of an antigen to allow antibody responses on revaccination) with vaccine directed toward an older avian influenza H5 strain might lead to secondary antibody responses to a single dose of more current H5 avian influenza vaccine.

Objectives: To assess priming with the older avian influenza A/Vietnam/1203/2004(H5N1) (Vietnam) vaccine and to conduct dose-response studies with vaccine directed against the more contemporary H5N1 avian influenza virus, influenza A/Anhui/01/2005 (Anhui).

Serological responses to an avian influenza A/H7N9 vaccine mixed at the point-of-use with MF59 adjuvant: a randomized clinical trial.

Importance: Human infections with avian influenza A/H7N9 have resulted in high morbidity and mortality in China.

Objective: To compare safety and immunogenicity of different doses of influenza A/Shanghai/2/13 (H7N9) vaccine mixed with or without the MF59 adjuvant.

Design, Setting, And Participants: Multicenter, randomized, double-blind, phase 2 trial at 4 US sites enrolled 700 adults aged 19 to 64 years beginning in September 2013; 6-month follow-up was completed in May 2014.

HSV-1 and HSV-2 seroprevalence in the united states among asymptomatic women unaware of any herpes simplex virus infection (Herpevac Trial for Women).

Objectives: Recent evidence suggests that the epidemiology of herpes simplex viruses (HSVs) is changing because fewer HSV-1 infections are acquired in childhood and increased sexual transmission of HSV-1 is reported. The objective of the study was to assess the seroprevalence of type-specific antibodies to HSV-1 and HSV-2 in the United States.

Methods: We used the Western blot antibody screening data from a large phase III vaccine efficacy trial (Herpevac Trial for Women) to assess the seroprevalence of type-specific antibodies to HSV-1 and HSV-2 in the United States.

Correlate of immune protection against HSV-1 genital disease in vaccinated women.

Background: Previously we conducted a double-blind controlled, randomized efficacy field trial of gD-2 HSV vaccine adjuvanted with ASO4 in 8323 women. Subjects had been previously selected to be seronegative for HSV-1 and HSV-2. We found that vaccine was 82% protective against HSV-1 genital disease, but offered no significant protection against HSV-2 genital disease.

Epidemiology, clinical presentation, and antibody response to primary infection with herpes simplex virus type 1 and type 2 in young women.

Background: Herpes simplex virus infections type 1 (HSV-1) and type 2 (HSV-2) are common, but the epidemiology of HSV disease is changing.

Methods: HSV-seronegative women, aged 18-30 years, who were in the control arm of the HERPEVAC Trial for Women were followed for 20 months for primary HSV infections.

Results: Of the 3438 evaluable participants, 183 became infected with HSV: 127 (3.