A role for immune modulation in achieving functional cure for chronic hepatitis B among current changes in the landscape of new treatments.

Introduction: Chronic hepatitis B (CHB) is rarely cured using available treatments. Barriers to cure are: 1) persistence of reservoirs of hepatitis B virus (HBV) replication and antigen production (HBV DNA); 2) high burden of viral antigens that promote T cell exhaustion with T cell dysfunction; 3) CHB-induced impairment of immune responses.

Areas Covered: We discuss options for new therapies that could address one or more of the barriers to functional cure, with particular emphasis on the potential role of immunotherapy.

Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection.

Background: A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease.

Methods: In this phase 1-2 randomized, double-blind, placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56.

MHC class II invariant chain-adjuvanted viral vectored vaccines enhances T cell responses in humans.

Strategies to enhance the induction of high magnitude T cell responses through vaccination are urgently needed. Major histocompatibility complex (MHC) class II-associated invariant chain (Ii) plays a critical role in antigen presentation, forming MHC class II peptide complexes for the generation of CD4 T cell responses. Preclinical studies evaluating the fusion of Ii to antigens encoded in vector delivery systems have shown that this strategy may enhance T cell immune responses to the encoded antigen.

A Novel Vaccine Strategy Employing Serologically Different Chimpanzee Adenoviral Vectors for the Prevention of HIV-1 and HCV Coinfection.

Nearly 3 million people worldwide are coinfected with HIV and HCV. Affordable strategies for prevention are needed. We developed a novel vaccination regimen involving replication-defective and serologically distinct chimpanzee adenovirus (ChAd3, ChAd63) vector priming followed by modified vaccinia Ankara (MVA) boosts, for simultaneous delivery of HCV non-structural (NSmut) and HIV-1 conserved (HIVconsv) region immunogens.

Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention.

Introduction: GSK has developed a two-dose adjuvanted recombinant zoster vaccine (Shingrix, RZV) to protect people aged ≥50 years (50+) against herpes zoster (HZ) and its complications. RZV showed >90% efficacy against HZ, sustained over 4 years of follow-up, in all studied age groups.

Areas Covered: This article reviews the scientific rationale underlying the design of RZV; the clinical evidence demonstrating immunogenicity, safety, and efficacy in persons 50+; and the public health implications and cost-effectiveness.

Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine versus one dose of monovalent varicella vaccine: a multicentre, observer-blind, randomised, controlled trial.

Background: Rates of varicella have decreased substantially in countries implementing routine varicella vaccination. Immunisation is possible with monovalent varicella vaccine or a combined measles-mumps-rubella-varicella vaccine (MMRV). We assessed protection against varicella in naive children administered one dose of varicella vaccine or two doses of MMRV.

A phase 1/2 clinical trial evaluating safety and immunogenicity of a varicella zoster glycoprotein e subunit vaccine candidate in young and older adults.

Background: An adjuvanted recombinant varicella zoster virus (VZV) subunit vaccine is being developed for the prevention of herpes zoster and its complications.

Methods: In a phase I/II, open-label, randomized, parallel-group study, older adults (50-70 years) received 2 doses 2 months apart of an adjuvanted recombinant glycoprotein E vaccine (HZ/su; n = 45), a live attenuated Oka strain VZV vaccine (OKA; n = 45), or HZ/su and OKA administered concomitantly (n = 45). To evaluate safety prior to administration in older adults, young adults (18-30 years) were vaccinated with 2 doses 2 months apart of HZ/su (n = 10) or OKA (n = 10).

Immunogenicity and protective efficacy in mice and hamsters of a β-propiolactone inactivated whole virus SARS-CoV vaccine.

The immunogenicity and efficacy of β-propiolactone (BPL) inactivated whole virion SARS-CoV (WI-SARS) vaccine was evaluated in BALB/c mice and golden Syrian hamsters. The vaccine preparation was tested with or without adjuvants. Adjuvant Systems AS01(B) and AS03(A) were selected and tested for their capacity to elicit high humoral and cellular immune responses to WI-SARS vaccine.

Comparative analysis of the complete nucleotide sequences of measles, mumps, and rubella strain genomes contained in Priorix-Tetra and ProQuad live attenuated combined vaccines.

Measles, mumps, and rubella are three common viral childhood diseases that can have serious complications. Active immunization against these diseases became possible with the development of live attenuated virus vaccines in the late 1960s. Vaccines against these three diseases were combined into trivalent (Priorix, GlaxoSmithKline Biologicals and M-M-R(II), Merck & Co.

Complete DNA sequences of two oka strain varicella-zoster virus genomes.

Varicella-zoster virus (VZV) is a herpesvirus and is the causative agent of chicken pox (varicella) and shingles (herpes zoster). Active immunization against varicella became possible with the development of live attenuated varicella vaccine. The Oka vaccine strain was isolated in Japan from a child who had typical varicella, and it was then attenuated by serial passages in cell culture.

A new quantitative RT-PCR method for sensitive detection of dengue virus in serum samples.

In order to detect and identify dengue serotypes in serum samples, we developed a single-step quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) assay (referred to as Q-PCR). Sets of primers were selected from the capsid region of the viral genome. Dengue serotypes 1/3 and 2/4 were detected in two separate duplex amplification reactions using specific primers and fluorogenic TaqMan probes.

The amino-terminal domain of bovine viral diarrhea virus Npro protein is necessary for alpha/beta interferon antagonism.

The alpha/beta interferon (IFN-alpha/beta) system is the first line of defense against viral infection and a critical link between the innate and adaptive immune responses. IFN-alpha/beta secretion is the hallmark of cellular responses to acute RNA virus infections. As part of their survival strategy, many viruses have evolved mechanisms to counteract the host IFN-alpha/beta response.

Detection and quantitation of bovine respiratory syncytial virus using real-time quantitative RT-PCR and quantitative competitive RT-PCR assays.

A single tube, fluorogenic probe-based, real-time quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) assay was developed for detection and quantitation of bovine respiratory syncytial virus (BRSV) using BioRad's iCycler iQ. Real-time Q-RT-PCR was compared with quantitative competitive RT-PCR (QC-RT-PCR) and viral titers. Viral mRNA levels were measured in BRSV-infected bovine turbinate cell lysate harvested at eight time points (1.

The envelope glycoprotein E2 is a determinant of cell culture tropism in ruminant pestiviruses.

Bovine viral diarrhoea virus (BVDV) isolates infect cultured Madin-Darby bovine kidney (MDBK) cells as efficiently as sheep kidney cells. In contrast, border disease virus (BDV) propagates poorly in MDBK cells but infects sheep cells very efficiently. The envelope glycoprotein E2 has been shown to be essential for virus infectivity.

Role of bovine viral diarrhea virus biotype in the establishment of fetal infections.

Objective: To examine the role of bovine viral diarrhea virus (BVDV) biotype on the establishment of fetal infection in cattle.

Animals: 30 mixed-breed pregnant cows.

Procedure: Pregnant cows were inoculated oronasally with either i-WNADL, originating from an infectious BVDV cDNA clone of the National Animal Disease Laboratory (NADL) isolate, or the parental virus stock, termed NADL-A.