Evaluation of a Live-Attenuated Human Parainfluenza Virus Type 2 Vaccine in Adults and Children.

We conducted a phase I clinical trial of the live-attenuated recombinant human parainfluenza virus type 2 (HPIV2) vaccine candidate rHPIV2-15C/948L/∆1724 sequentially in adults, HPIV2-seropositive children, and HPIV2-seronegative children, the target population for vaccination. rHPIV2-15C/948L/∆1724 was appropriately restricted in replication in adults and HPIV2-seropositive children but was overattenuated for HPIV2-seronegative children.

Epidemiology of Human Parainfluenza Virus Type 3 and Respiratory Syncytial Virus Infections in the Time of Coronavirus Disease 2019: Findings From a Household Cohort in Maryland.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, human parainfluenza type 3 (HPIV-3) and respiratory syncytial virus (RSV) circulation increased as nonpharmaceutical interventions were relaxed. Using data from 175 households (n = 690 members) followed between November 2020 and October 2021, we characterized HPIV-3 and RSV epidemiology in children aged 0-4 years and their households.

Methods: Households with ≥1 child aged 0-4 years were enrolled; members collected weekly nasal swabs (NS) and additional NS with respiratory illnesses (RI).

Live-attenuated Vaccines Prevent Respiratory Syncytial Virus-associated Illness in Young Children.

Active immunization is needed to protect infants and young children against respiratory syncytial virus (RSV). Rationally designed live-attenuated RSV vaccines are in clinical development. Develop preliminary estimates of vaccine efficacy, assess durability of antibody responses to vaccination and "booster" responses after natural RSV infection, and determine sample sizes needed for more precise estimates of vaccine efficacy.

Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine RSV/ΔNS2/Δ1313/I1314L in RSV-Seronegative Children.

Background: Respiratory syncytial virus (RSV) is the leading global cause of severe pediatric acute respiratory tract illness, and a vaccine is needed. RSV/ΔNS2/Δ1313/I1314L contains 2 attenuating elements: (1) deletion of the interferon antagonist NS2 gene and (2) deletion of codon 1313 of the RSV polymerase gene and the stabilizing missense mutation I1314L. This live vaccine candidate was temperature-sensitive, genetically stable, replication restricted, and immunogenic in nonhuman primates.

Evaluation of a Live Attenuated Human Metapneumovirus Vaccine in Adults and Children.

We conducted a phase I clinical trial of an experimental live attenuated recombinant human metapneumovirus (HMPV) vaccine (rHMPV-Pa) sequentially in adults, HMPV-seropositive children, and HMPV-seronegative children, the target population for vaccination. rHMPV-Pa was appropriately restricted in replication in adults and HMPV-seropositive children but was overattenuated for HMPV-seronegative children.

The live attenuated chimeric vaccine rWN/DEN4Δ30 is well-tolerated and immunogenic in healthy flavivirus-naïve adult volunteers.

WNV has become the leading vector-borne cause of meningoencephalitis in the United States. Although the majority of WNV infections result in asymptomatic illness, approximately 20% of infections result in West Nile fever and 1% in West Nile neuroinvasive disease (WNND), which causes encephalitis, meningitis, or flaccid paralysis. The elderly are at particular risk for WNND, with more than half the cases occurring in persons older than sixty years of age.

A single dose of any of four different live attenuated tetravalent dengue vaccines is safe and immunogenic in flavivirus-naive adults: a randomized, double-blind clinical trial.

Background: Dengue virus (DENV) causes hundreds of millions of infections annually. Four dengue serotypes exist, and previous infection with one serotype increases the likelihood of severe disease with a second, heterotypic DENV infection.

Methods: In a randomized, placebo-controlled study, the safety and immunogenicity of 4 different admixtures of a live attenuated tetravalent (LATV) dengue vaccine were evaluated in 113 flavivirus-naive adults.

A single dose of the DENV-1 candidate vaccine rDEN1Δ30 is strongly immunogenic and induces resistance to a second dose in a randomized trial.

Dengue is an emerging infectious disease that has become the most important arboviral infection worldwide. There are four serotypes of dengue virus, DENV-1, DENV-2, DENV-3, and DENV-4, each capable of causing the full spectrum of disease. rDEN1Δ30 is a live attenuated investigational vaccine for the prevention of DENV-1 illness and is also a component of an investigational tetravalent DENV vaccine currently in Phase I evaluation.

Heterotypic dengue infection with live attenuated monotypic dengue virus vaccines: implications for vaccination of populations in areas where dengue is endemic.

Background: Because infection with any of the 4 Dengue virus serotypes may elicit both protective neutralizing antibodies and nonneutralizing antibodies capable of enhancing subsequent heterotypic Dengue virus infections, the greatest risk for severe dengue occurs during a second, heterotypic Dengue virus infection. It remains unclear whether the replication of live attenuated vaccine viruses will be similarly enhanced when administered to Dengue-immune individuals.

Methods: We recruited 36 healthy adults who had previously received a monovalent live Dengue virus vaccine 0.

Phase I clinical evaluation of rDEN4Delta30-200,201: a live attenuated dengue 4 vaccine candidate designed for decreased hepatotoxicity.

The rDEN4Delta30-200,201 is a live attenuated DENV-4 vaccine candidate specifically designed to further attenuate the rDEN4Delta30 parent virus. In the present study, 28 healthy adult volunteers were randomized to receive either 10(5) plaque-forming unit (PFU) of vaccine (20) or placebo (8) as a single subcutaneous injection. Volunteers were evaluated for safety every other day for 16 days.

Phenotyping of peripheral blood mononuclear cells during acute dengue illness demonstrates infection and increased activation of monocytes in severe cases compared to classic dengue fever.

In vitro studies have attempted to identify dengue virus (DEN) target cells in peripheral blood; however, extensive phenotyping of peripheral blood mononuclear cells (PBMCs) from dengue patients has not been reported. PBMCs collected from hospitalized children suspected of acute dengue were analyzed for DEN prM, CD32, CD86, CD14, CD11c, CD16, CD209, CCR7, CD4, and CD8 by flow cytometry to detect DEN antigen in PBMCs and to phenotype DEN-positive cells. DEN prM was detected primarily in activated monocytes (CD14(+), CD32(+), CD86(+), CD11c(+)).

rDEN2/4Delta30(ME), a live attenuated chimeric dengue serotype 2 vaccine is safe and highly immunogenic in healthy dengue-naïve adults.

rDEN2/4Delta30(ME) is an attenuated chimeric dengue virus in which the prM and E structural proteins of the DEN4 candidate vaccine rDEN4Delta30 have been replaced by those of the prototypic DEN2 NGC virus. rDEN2/4Delta30(ME) was evaluated at a dose of 1,000 PFU in 20 healthy dengue-naïve adult volunteers. Eight volunteers received placebo.