Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: A randomised, comparator-controlled, phase 2 trial.

Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and lower-middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A public sector manufacturer in Vietnam assessed the immunogenicity of NDV-HXP-S (COVIVAC) relative to an authorized vaccine.

Measles-Rubella Microarray Patches Phase III Clinical Trial Framework: Proposal and Considerations.

: The Measles-Rubella Microarray Patch (MR-MAP) is an important technology that is expected to reduce coverage and equity gaps for measles-containing vaccines (MCVs), reach zero-dose children, and contribute to elimination of measles and rubella. MR-MAPs are anticipated to be easier to deploy programmatically and could be delivered by lesser-trained health workers, thereby increasing immunization coverage. The most advanced MR-MAP has reached clinical proof-of-concept through a Phase I/II trial in the target population of infants and young children.

A chimeric haemagglutinin-based universal influenza virus vaccine boosts human cellular immune responses directed towards the conserved haemagglutinin stalk domain and the viral nucleoprotein.

Background: The development of a universal influenza virus vaccine, to protect against both seasonal and pandemic influenza A viruses, is a long-standing public health goal. The conserved stalk domain of haemagglutinin (HA) is a promising vaccine target. However, the stalk is immunosubdominant.

Effective and safe transfer of maternal antibodies persisting two months postpartum following maternal immunization with different doses of recombinant pertussis-containing vaccines.

Introduction: Recombinant acellular pertussis (ap) vaccines containing genetically inactivated pertussis toxin (PT) and filamentous hemagglutinin (FHA) with or without tetanus (TT) and diphtheria (DT) vaccines (Td) were found safe and immunogenic in non-pregnant and pregnant women. We report here maternal antibody transfer and safety data in mothers and neonates.

Methods: This is the follow up of a phase 2 trial in 2019 among 400 pregnant women who randomly received one dose of recombinant pertussis-only vaccine containing 1 µg PT and 1 µg FHA (ap1), or Td combined with ap1 (Tdap1), or with 2 µg PT and 5 µg FHA (Tdap2), or with 5 µg PT and 5 µg FHA (TdaP5 Boostagen®, BioNet, Thailand) or chemically-inactivated acellular pertussis comparator (Tdap8 Boostrix™, GSK, Belgium), either in the second or third trimester of gestation.

A phase 2 randomized controlled dose-ranging trial of recombinant pertussis booster vaccines containing genetically inactivated pertussis toxin in pregnant women.

Introduction: Despite a decrease in infections caused by Bordetella pertussis due to COVID-19 pandemic, booster vaccination of pregnant women is still recommended to protect newborns. Highly immunogenic vaccines containing genetically inactivated pertussis toxin (PT) and filamentous hemagglutinin (FHA) may generate comparable anti-PT antibody concentrations, even at lower doses, to chemically inactivated acellular pertussis vaccines (Tdap) shown effective for maternal immunization.

Methods: This phase 2 randomized, observer-blind, active-controlled non-inferiority trial was conducted in healthy Thai pregnant women randomly assigned to receive one dose of low-dose recombinant pertussis-only vaccine containing 1 µg PT and 1 µg FHA (ap1), or tetanus, reduced-dose diphtheria combined with ap1 (Tdap1), or combined with 2 µg PT and 5 µg FHA (Tdap2), or with 5 µg PT and 5 µg FHA (TdaP5, Boostagen®) or comparator containing 8 µg of chemically inactivated pertussis toxoid, 8 µg FHA, and 2.

Influenza A(H7N9) Pandemic Preparedness: Assessment of the Breadth of Heterologous Antibody Responses to Emerging Viruses from Multiple Pre-Pandemic Vaccines and Population Immunity.

Influenza A(H7N9) viruses remain as a high pandemic threat. The continued evolution of the A(H7N9) viruses poses major challenges in pandemic preparedness strategies through vaccination. We assessed the breadth of the heterologous neutralizing antibody responses against the 3rd and 5th wave A(H7N9) viruses using the 1st wave vaccine sera from 4 vaccine groups: 1.

Vital sign predictors of severe influenza among children in an emergent care setting.

Background: Decisions regarding the evaluation of children with influenza infection rely on the likelihood of severe disease. The role of early vital signs as predictors of severe influenza infection in children is not well known. Our objectives were to determine the value of vital signs in predicting hospitalization/recurrent emergency department (ED) visits due to influenza infection in children.

Safety and immunogenicity of an egg-based inactivated Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Interim results of a randomized, placebo-controlled, phase 1/2 trial in Vietnam.

Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus (NDV) vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Wuhan-Hu-1. The spike protein was stabilized and incorporated into NDV virions by removing the polybasic furin cleavage site, introducing the transmembrane domain and cytoplasmic tail of the fusion protein of NDV, and introducing six prolines for stabilization in the prefusion state.

Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Interim results of a randomised, placebo-controlled, phase 1 trial.

Background: Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed by public sector manufacturers in Thailand, Vietnam, and Brazil; herein are initial results from Thailand.

WHO preferred product characteristics for monoclonal antibodies for passive immunization against respiratory syncytial virus (RSV) disease in infants - Key considerations for global use.

World Health Organization (WHO) preferred product characteristics describe preferences for product attributes that would help optimize value and use to address global public health needs, with a particular focus on low- and middle-income countries. Having previously published preferred product characteristics for both maternal and paediatric respiratory syncytial virus (RSV) vaccines, WHO recently published preferred product characteristics for monoclonal antibodies to prevent severe RSV disease in infants. This article summarizes the key attributes from the preferred product characteristics and discusses key considerations for future access and use of preventive RSV monoclonal antibodies.

Association Between Hemagglutination Inhibition Antibody Titers and Protection Against Reverse-Transcription Polymerase Chain Reaction-Confirmed Influenza Illness in Children 6-35 Months of Age: Statistical Evaluation of a Correlate of Protection.

Background: Data from a randomized controlled efficacy trial of an inactivated quadrivalent influenza vaccine in children 6-35 months of age were used to determine whether hemagglutination inhibition (HI) antibody titer against A/H1N1 and A/H3N2 is a statistical correlate of protection (CoP) for the risk of reverse-transcription polymerase chain reaction (RT-PCR)-confirmed influenza associated with the corresponding strain.

Methods: The Prentice criteria were used to statistically validate strain-specific HI antibody titer as a CoP. The probability of protection was identified using the Dunning model corresponding to a prespecified probability of protection at an individual level.

A phase 2 randomized controlled dose-ranging trial of recombinant pertussis booster vaccines containing genetically inactivated pertussis toxin in women of childbearing age.

Background: A phase 2 randomized-controlled safety and immunogenicity trial evaluating different doses of recombinant acellular pertussis vaccine containing genetically-inactivated pertussis toxin (PT) was conducted in women of childbearing age in Thailand to identify formulations to advance to a trial in pregnant women.

Methods: A total of 250 women were randomized 1:1:1:1:1 to receive one dose of one of three investigational vaccines including low-dose recombinant pertussis-only vaccine containing 1 μg PT and 1 μg FHA (ap1), tetanus, reduced-dose diphtheria (Td) combined to ap1 (Tdap1) or combined to recombinant pertussis containing 2 μg PT and 5 μg FHA (Tdap2), or one dose of licensed recombinant TdaP vaccine containing 5 μg PT and 5 μg FHA (Boostagen®, TdaP5) or licensed Tdap vaccine containing 8 μg of chemically inactivated pertussis toxoid (PT), 8 μg FHA, and 2.5 μg pertactin (PRN) (Boostrix, Tdap8).

A Newcastle disease virus expressing a stabilized spike protein of SARS-CoV-2 induces protective immune responses.

Rapid development of COVID-19 vaccines has helped mitigating SARS-CoV-2 spread, but more equitable allocation of vaccines is necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine candidate based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here, we show that the NDV vector expressing an optimized spike antigen (NDV-HXP-S) is a versatile vaccine inducing protective antibody responses.

Safety and Immunogenicity of an Inactivated Recombinant Newcastle Disease Virus Vaccine Expressing SARS-CoV-2 Spike: Interim Results of a Randomised, Placebo-Controlled, Phase 1/2 Trial.

Background: Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed in Thailand, Vietnam, and Brazil; herein are initial results from Thailand.

Immunogenicity and Safety of AS03-adjuvanted H5N1 Influenza Vaccine in Children 6-35 Months of Age: Results From a Phase 2, Randomized, Observer-blind, Multicenter, Dose-ranging Study.

Background: This phase 2 observer-blind, randomized, multicenter, dose-ranging study evaluated immunogenicity and safety of different formulations of an AS03-adjuvanted H5N1 influenza vaccine in children 6-35 months of age.

Methods: One hundred eighty-five children randomized into 5 groups [1.9 µg hemagglutinin (HA)/AS03B, 0.

Historical Analysis of the Risk of Hepatitis E and Its Complications in Pregnant Women in Nepal, 1996-1998.

Hepatitis E (HE) during pregnancy can be fatal; there are no prospective risk estimates for HE and its complications during pregnancy. We followed 2,404 pregnant women for HE and pregnancy outcomes from 1996 to 1998. Subjects from Nepal were enrolled at an antenatal clinic with pregnancy of ≤ 24 weeks.

Hybrid imaging of complicating osteomyelitis in the peripheral skeleton.

Diagnosing complicating osteomyelitis (COM) is clinically challenging. Laboratory tests are of limited utility, and other than isolation of the offending organism, diagnostic imaging tests are of paramount importance. Nuclear Medicine techniques play an important role in noninvasive evaluation of osteomyelitis, using both single-photon emission tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals.

AS03-adjuvanted H7N9 inactivated split virion vaccines induce cross-reactive and protective responses in ferrets.

Human infections with avian H7N9 subtype influenza viruses are a major public health concern and vaccines against H7N9 are urgently needed for pandemic preparedness. In early 2013, novel H7N9 influenza viruses emerged in China that caused about 1600 human cases of infection with a high associated case fatality rate. In this study, two H7N9 split virion vaccines with or without AS03 adjuvant were tested in the naive ferret model.

Immunogenicity and safety of a novel ten-valent pneumococcal conjugate vaccine in healthy infants in The Gambia: a phase 3, randomised, double-blind, non-inferiority trial.

Background: An affordable pneumococcal conjugate vaccine (PCV) is needed to ensure sustainable access in low-income and middle-income countries. This trial examined the immunogenicity and safety of a novel ten-valent PCV (SIIPL-PCV) containing serotypes 1, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, and 23F compared with the pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV; Synflorix; GlaxoSmithKline; Brentford, UK).

Methods: In this single-centre, randomised, double-blind, phase 3, non-inferiority trial in The Gambia, healthy, PCV-naive infants aged 6-8 weeks were enrolled and assigned using permuted block randomisation to receive one of three lots of SIIPL-PCV or to PHiD-CV in a ratio of 2:2:2:3.

Chimeric Hemagglutinin-Based Live-Attenuated Vaccines Confer Durable Protective Immunity against Influenza A Viruses in a Preclinical Ferret Model.

Epidemic or pandemic influenza can annually cause significant morbidity and mortality in humans. We developed novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccines, which contain a conserved HA stalk domain from a 2009 pandemic H1N1 (pH1N1) strain combined with globular head domains from avian influenza A viruses. Our previous reports demonstrated that prime-boost sequential immunizations induced robust antibody responses directed toward the conserved HA stalk domain in ferrets.

A Newcastle Disease Virus (NDV) Expressing a Membrane-Anchored Spike as a Cost-Effective Inactivated SARS-CoV-2 Vaccine.

A successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine must not only be safe and protective, but must also meet the demand on a global scale at a low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent coronavirus disease 2019 (COVID-19) vaccine in mice and hamsters.

A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial.

Seasonal influenza viruses constantly change through antigenic drift and the emergence of pandemic influenza viruses through antigenic shift is unpredictable. Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps pandemic preparedness.

A Newcastle disease virus (NDV) expressing membrane-anchored spike as a cost-effective inactivated SARS-CoV-2 vaccine.

A successful SARS-CoV-2 vaccine must be not only safe and protective but must also meet the demand on a global scale at low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent COVID-19 vaccine in mice and hamsters.