Efficacy of a monovalent (D614) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, multi-country study.

Background: The literature on first generation COVID-19 vaccines show they were less effective against new SARS-CoV-2 variants of concern including Omicron (BA.1, BA.2, BA.

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, parallel, randomised, modified double-blind, placebo-controlled trial.

Background: COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern. This study aimed to describe the clinical efficacy and safety of a bivalent SARS-CoV-2 recombinant protein vaccine as a two-injection primary series during a period of circulation of the omicron (B.1.

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 Protein Vaccine.

Background: COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern.

Methods: We conducted a global Phase 3, multi-stage efficacy study (NCT04904549) among adults aged ≥18 years. Participants were randomized 1:1 to receive two intramuscular injections 21 days apart of a bivalent SARS-CoV-2 recombinant protein vaccine with AS03-adjuvant (5 μg of ancestral (D614) and 5 μg of B.

Accuracy and efficacy of pre-dengue vaccination screening for previous dengue infection with a new dengue rapid diagnostic test: a retrospective analysis of phase 3 efficacy trials.

Background: A dengue pre-vaccination test that is convenient, highly specific, and highly sensitive is still needed. The OnSite Dengue IgG rapid diagnostic test (RDT) is a new rapid diagnostic test specifically designed for pre-vaccination screening. We aimed to retrospectively assess the efficacy of a tetravalent dengue vaccine (CYD-TDV) in participants determined to be dengue seropositive by the OnSite IgG RDT and to evaluate assay performances.

Analysis of Hospitalized and Severe Dengue Cases Over the 6 years of Follow-up of the Tetravalent Dengue Vaccine (CYD-TDV) Efficacy Trials in Asia and Latin America.

Background: CYD-TDV, a live, attenuated, tetravalent dengue vaccine, has been approved for the prevention of symptomatic dengue in previously dengue exposed individuals. This post hoc analysis assessed hospitalized and severe virologically confirmed dengue (VCD) over the complete 6-year follow-up of 3 CYD-TDV efficacy studies (CYD14, CYD15, and CYD23/CYD57).

Methods: The main outcomes were hazard ratios (HRs) for hospitalized or severe VCD by baseline dengue serostatus, focusing on those who were seropositive, and by age at immunization (<9 years/≥9 years).

Immunobridging efficacy of a tetravalent dengue vaccine against dengue and against hospitalized dengue from children/adolescents to adults in highly endemic countries.

Background: The recombinant tetravalent live-attenuated dengue vaccine based on the YF 17D vaccine virus backbone (CYD-TDV) demonstrated vaccine efficacy (VE) against symptomatic, virologically confirmed dengue of any serotype from month 13 to month 25 (VCD-DENV-AnyM13→M25) in the CYD14 (2-14-y-olds) and CYD15 (9-16-y-olds) phase 3 trials. Fifty percent plaque reduction neutralization test (PRNT50) titers are a potential surrogate for immunobridging VE to adults.

Methods: Using PRNT50 calibration datasets, we applied immunobridging approaches using baseline and/or M13 PRNT50 titers to estimate VE against VCD-DENV-AnyM0→M25 and against hospitalized VCD (HVCD)-DENV-AnyM0→M72 in hypothetical 18-45-y-old and 46-50-y-old CYD14 and CYD15 cohorts.

Accuracy and efficacy of pre-dengue vaccination screening for previous dengue infection with five commercially available immunoassays: a retrospective analysis of phase 3 efficacy trials.

Background: The tetravalent dengue vaccine (CYD-TDV) has been shown to provide protection against dengue disease over 5-year follow-up in participants with previous dengue infection, but increased the risk of dengue hospitalisation and severe dengue during long-term follow-up in those without previous dengue infection. WHO recommended pre-vaccination screening to identify those with previous dengue infection (ie, dengue seropositive) who would benefit from vaccination. We re-evaluated CYD-TDV efficacy in those identified as dengue seropositive using five commercially available immunoassays, and assessed immunoassay performance.

Zika and Dengue Interactions in the Context of a Large Dengue Vaccine Clinical Trial in Latin America.

A phase III dengue vaccine trial including 9- to 16-year-olds in Latin America (NCT01374516) was ongoing at the time of a Zika outbreak. We explored interactions between dengue and Zika, in the context of dengue vaccination. Symptomatic virologically confirmed Zika (VCZ) was evaluated using acute-phase sera from febrile participants (January 2013-March 2018).

Efficacy after 1 and 2 doses of CYD-TDV in dengue endemic areas by dengue serostatus.

A simplified dose regimen of the live, attenuated, tetravalent dengue vaccine (CYD-TDV) could have the potential to facilitate easier implementation of immunization programs against symptomatic virologically-confirmed dengue (VCD) in dengue seropositive individuals aged ≥ 9 years. This post-hoc analysis of two Phase III studies (CYD14 [NCT01373281] and CYD15 [NCT01374516]) in dengue endemic areas assessed the efficacy of CYD-TDV by dengue serostatus between dose 1 and 2 (at Month [M] 6), between dose 2 and 3 (at M12), and from dose 3 to M25. Baseline dengue serostatus (seropositive or seronegative) was determined based on measured dengue neutralizing antibody titers with the 50% plaque reduction neutralization test (PRNT) or ascertained by logistic regression-based multiple imputation (MI) to predict PRNT.

Assessment of the long-term efficacy of a dengue vaccine against symptomatic, virologically-confirmed dengue disease by baseline dengue serostatus.

CYD-TDV is a live, attenuated, tetravalent dengue vaccine licensed in 21 countries. We undertook a post-hoc analysis of the long-term efficacy of CYD-TDV during the surveillance expansion phase (SEP) of two Phase III studies (CYD14 in the Asia-Pacific region; CYD15 in Latin America). The SEP included approximately Year 5 and the entire Year 6 of follow-up after the first study injection.

Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials.

A recombinant live attenuated tetravalent dengue vaccine (CYD-TDV) has been shown to be efficacious in preventing virologically-confirmed dengue disease, severe dengue disease and dengue hospitalization in children aged 2-16 years in Asia and Latin America. We analyzed pooled safety data from 18 phase I, II and III clinical trials in which the dengue vaccine was administered to participants aged 2-60 years, including long-term safety follow-up in three efficacy trials. The participants were analyzed according to their age at enrollment.

Staphylococcus aureus: the current state of disease, pathophysiology and strategies for prevention.

Staphylococcus aureus is both a commensal organism and also an important opportunistic human pathogen, causing a variety of community and hospital-associated pathologies, such as bacteremia-sepsis, endocarditis, pneumonia, osteomyelitis, arthritis and skin diseases. The resurgence of S. aureus during the last decade in many settings has been facilitated not only by bacterial antibiotic resistance mechanisms but also by the emergence of new S.

Assessment of bivalent and tetravalent dengue vaccine formulations in flavivirus-naïve adults in Mexico.

Unlabelled: Several ChimeriVax-Dengue (CYD)-based vaccination strategies were investigated as potential alternatives to vaccination with tetravalent CYD vaccine (CYD-TDV) in this phase IIa trial conducted in 2008-9 in 150 healthy adults. Participants were randomized and vaccinated on D0 and D105 (± 15 days). One group received bivalent CYD vaccine against serotypes 1 and 3 (CYD-1;3) on day 0 and CYD-2;4 on day 105 (± 15 days).

Efficacy of a tetravalent dengue vaccine in children in Latin America.

Background: In light of the increasing rate of dengue infections throughout the world despite vector-control measures, several dengue vaccine candidates are in development.

Methods: In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic, we randomly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and 12 under blinded conditions. The children were then followed for 25 months.

Preclinical and clinical development of a YFV 17 D-based chimeric vaccine against West Nile virus.

Substantial success has been achieved in the development and implementation of West Nile (WN) vaccines for horses; however, no human WN vaccines are approved. This review focuses on the construction, pre-clinical and clinical characterization of ChimeriVax-WN02 for humans, a live chimeric vaccine composed of a yellow fever (YF) 17D virus in which the prM-E envelope protein genes are replaced with the corresponding genes of the WN NY99 virus. Pre-clinical studies demonstrated that ChimeriVax-WN02 was significantly less neurovirulent than YF 17D in mice and rhesus and cynomolgus monkeys.

Immunogenicity and safety of a recombinant tetravalent dengue vaccine in children and adolescents ages 9-16 years in Brazil.

Immunogenicity and safety of a recombinant, live-attenuated, tetravalent dengue disease vaccine (CYD-TDV) was evaluated in children/adolescents in Brazil. In this observer-blind, placebo-controlled, phase II single-center study, children/adolescents (ages 9-16 years) were randomized to receive CYD-TDV or placebo at 0, 6, and 12 months. Immunogenicity was assessed using a 50% plaque neutralization test.

Safety and immunogenicity of a recombinant tetravalent dengue vaccine in 9-16 year olds: a randomized, controlled, phase II trial in Latin America.

Background: The dengue virus is a member of the Flavivirus (FV) genus, which also includes the yellow fever virus. Dengue disease is caused by any 1 of 4 dengue virus serotypes and is a serious public health concern in Latin America. This study evaluated the safety and immunogenicity of a candidate recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) in 9-16 year olds in Latin America.

Safety and immunogenicity of three tetravalent dengue vaccine formulations in healthy adults in the USA.

Background: A candidate recombinant, live-attenuated, CYD tetravalent dengue vaccine (CYD-TDV) has recently demonstrated immunogenicity, efficacy and good tolerability. This study was performed to evaluate three CYD-TDV formulations in adults.

Methods: This was a randomized, double-blind, multicenter, phase II trial.

The history of dengue outbreaks in the Americas.

Dengue is a viral disease usually transmitted by Aedes aegypti mosquitoes. Dengue outbreaks in the Americas reported in medical literature and to the Pan American Health Organization are described. The outbreak history from 1600 to 2010 was categorized into four phases: Introduction of dengue in the Americas (1600-1946); Continental plan for the eradication of the Ae.

Phase II, dose ranging study of the safety and immunogenicity of single dose West Nile vaccine in healthy adults ≥ 50 years of age.

Introduction: ChimeriVax-WN02 is a live, attenuated chimeric vaccine for protection against West Nile virus (WNV) produced by insertion of the genes encoding the pre-membrane (prM) and envelope (E) proteins of WNV (strain NY99) into the yellow fever 7D vaccine virus. This Phase II, randomized, double-blind, placebo-controlled, multi-center study in the US assessed the immunogenicity, viremia, and safety of the ChimeriVax-WN02 vaccine.

Methods: The study included adults in general good health.

Mumps antibody levels among students before a mumps outbreak: in search of a correlate of immunity.

Background: In 2006, a mumps outbreak occurred on a university campus despite ≥ 95% coverage of students with 2 doses of measles-mumps-rubella (MMR) vaccine. Using plasma samples from a blood drive held on campus before identification of mumps cases, we compared vaccine-induced preoutbreak mumps antibody levels between individuals who developed mumps (case patients) and those who did not develop mumps (nonpatients).

Methods: Preoutbreak samples were available from 11 case patients, 22 nonpatients who reported mumps exposure but no mumps symptoms, and 103 nonpatients who reported no known exposure and no symptoms.

Economic impact of dengue illness in the Americas.

The growing burden of dengue in endemic countries and outbreaks in previously unaffected countries stress the need to assess the economic impact of this disease. This paper synthesizes existing studies to calculate the economic burden of dengue illness in the Americas from a societal perspective. Major data sources include national case reporting data from 2000 to 2007, prospective cost of illness studies, and analyses quantifying underreporting in national routine surveillance systems.

Seroprevalence of antibody to mumps virus in the US population, 1999-2004.

Background: In 2006, the largest mumps outbreak in the United States in 20 years occurred. To understand prior mumps seroprevalence and factors associated with the presence of antibody to mumps virus, data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) were analyzed.

Methods: A mumps virus-specific enzyme immunoassay was used to measure the seroprevalence of serum immunoglobulin G (IgG) antibody among NHANES participants aged 6-49 years.

Guidance for isolation precautions for mumps in the United States: a review of the scientific basis for policy change.

The 2006 mumps resurgence in the United States raised questions about the appropriate isolation period for people with mumps. To determine the scientific basis for isolation recommendations, we conducted a literature review and considered isolation of virus and virus load in saliva and respiratory secretions as factors that were related to mumps transmission risk. Although mumps virus has been isolated from 7 days before through 8 days after parotitis onset, the highest percentage of positive isolations and the highest virus loads occur closest to parotitis onset and decrease rapidly thereafter.

The epidemiology of dengue in the americas over the last three decades: a worrisome reality.

We have reported the epidemic patterns of dengue disease in the Region of the Americas from 1980 through 2007. Dengue cases reported to the Pan American Health Organization were analyzed from three periods: 1980-1989 (80s), 1990-1999 (90s), and 2000-2007 (2000-7). Age distribution data were examined from Brazil, Venezuela, Honduras, and Mexico.