A Novel Neuraminidase Virus-Like Particle Vaccine Offers Protection Against Heterologous H3N2 Influenza Virus Infection in the Porcine Model.

Influenza A viruses (IAVs) pose a global health threat, contributing to hundreds of thousands of deaths and millions of hospitalizations annually. The two major surface glycoproteins of IAVs, hemagglutinin (HA) and neuraminidase (NA), are important antigens in eliciting neutralizing antibodies and protection against disease. However, NA is generally ignored in the formulation and development of influenza vaccines. In this study, we evaluate the immunogenicity and efficacy against challenge of a novel NA virus-like particles (VLPs) vaccine in the porcine model. We developed an NA2 VLP vaccine containing the NA protein from A/Perth/16/2009 (H3N2) and the matrix 1 (M1) protein from A/MI/73/2015, formulated with a water-in-oil-in-water adjuvant. Responses to NA2 VLPs were compared to a commercial adjuvanted quadrivalent whole inactivated virus (QWIV) swine IAV vaccine. Animals were prime boost vaccinated 21 days apart and challenged four weeks later with an H3N2 swine IAV field isolate, A/swine/NC/KH1552516/2016. Pigs vaccinated with the commercial QWIV vaccine demonstrated high hemagglutination inhibition (HAI) titers but very weak anti-NA antibody titers and subsequently undetectable NA inhibition (NAI) titers. Conversely, NA2 VLP vaccinated pigs demonstrated undetectable HAI titers but high anti-NA antibody titers and NAI titers. Post-challenge, NA2 VLPs and the commercial QWIV vaccine showed similar reductions in virus replication, pulmonary neutrophilic infiltration, and lung inflammation compared to unvaccinated controls. These data suggest that anti-NA immunity following NA2 VLP vaccination offers comparable protection to QWIV swine IAV vaccines inducing primarily anti-HA responses.

The incidence, prevalence and clinical features of MECP2 duplication syndrome in Australian children.

AIM: The aim of this study was to assess the incidence and prevalence of MECP2 duplication syndrome in Australian children and further define its phenotype. METHODS: The Australian Paediatric Surveillance Unit was used to identify children with MECP2 duplication syndrome between June 2014 and November 2017. Reporting clinicians were invited to complete a questionnaire. Clinician data (n = 20) were supplemented with information from the International Rett Syndrome Phenotype Database and from caregivers (n = 7). Birth prevalence and diagnostic incidence were calculated. RESULTS: The birth prevalence of MECP2 duplication syndrome in Australia was 0.65/100 000 for all live births and 1/100 000 for males. Diagnostic incidence was 0.07/100 000 person-years overall and 0.12/100 000 person-years for males. The median age at diagnosis was 23.5 months (range 0 months-13 years). A history of pneumonia was documented in three quarters of the clinical cases, half of whom had more than nine episodes. Cardiovascular abnormalities were reported in three cases. A clinical vignette is presented for one child who died due to severe idiopathic pulmonary hypertension. The majority (13/15) of males had inherited the duplication from their mothers, and two had an unbalanced translocation. CONCLUSIONS: MECP2 duplication syndrome is a rare but important diagnosis in children because of the burden of respiratory illness and recurrence risk. Pulmonary hypertension is a rare life-threatening complication. Array comparative genomic hybridisation testing is recommended for children with undiagnosed intellectual disability or global developmental delay. Early cardiac assessment and ongoing monitoring is recommended for MECP2 duplication syndrome.