A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques

The deployment of a vaccine that limits transmission and disease likely will be required to end the coronavirus disease 2019 (COVID-19) pandemic. We recently described the protective activity of an intranasally administered chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike (S) protein (ChAd-SARS-CoV-2-S [chimpanzee adenovirus-severe acute respiratory syndrome-coronavirus-2-S]) in the upper and lower respiratory tracts of mice expressing the human angiotensin-converting enzyme 2 (ACE2) receptor. Here, we show the immunogenicity and protective efficacy of this vaccine in non-human primates. Rhesus macaques were immunized with ChAd-Control or ChAd-SARS-CoV-2-S and challenged 1 month later by combined intranasal and intrabronchial routes with SARS-CoV-2. A single intranasal dose of ChAd-SARS-CoV-2-S induces neutralizing antibodies and T cell responses and limits or prevents infection in the upper and lower respiratory tracts after SARS-CoV-2 challenge. As ChAd-SARS-CoV-2-S confers protection in non-human primates, it is a promising candidate for limiting SARS-CoV-2 infection and transmission in humans

Utility of the Health of the Nation Outcome Scales (HoNOS) in Predicting Mental Health Service Costs for Patients with Common Mental Health Problems : Historical Cohort Study

BACKGROUND: Few countries have made much progress in implementing transparent and efficient systems for the allocation of mental health care resources. In England there are ongoing efforts by the National Health Service (NHS) to develop mental health 'payment by results' (PbR). The system depends on the ability of patient 'clusters' derived from the Health of the Nation Outcome Scales (HoNOS) to predict costs. We therefore investigated the associations of individual HoNOS items and the Total HoNOS score at baseline with mental health service costs at one year follow-up.METHODS: An historical cohort study using secondary care patient records from the UK financial year 2012-2013. Included were 1,343 patients with 'common mental health problems', represented by ICD-10 disorders between F32-48. Costs were based on patient contacts with community-based and hospital-based mental health services. The costs outcome was transformed into 'high costs' vs 'regular costs' in main analyses.RESULTS: After adjustment for covariates, 11 HoNOS items were not associated with costs. The exception was 'self-injury' with an odds ratio of 1.41 (95% CI 1.10-2.99). Population attributable fractions (PAFs) for the contribution of HoNOS items to high costs ranged from 0.6% (physical illness) to 22.4% (self-injury). After adjustment, the Total HoNOS score was not associated with costs (OR 1.03, 95% CI 0.99-1.07). However, the PAF (33.3%) demonstrated that it might account for a modest proportion of the incidence of high costs.CONCLUSIONS: Our findings provide limited support for the utility of the self-injury item and Total HoNOS score in predicting costs. However, the absence of associations for the remaining HoNOS items indicates that current PbR clusters have minimal ability to predict costs, so potentially contributing to a misallocation of NHS resources across England. The findings may inform the development of mental health payment systems internationally, especially since the vast majority of countries have not progressed past the early stages of this development. Discrepancies between our findings with those from Australia and New Zealand point to the need for further international investigations

Immunological correlates of protection afforded by PHV02 live, attenuated recombinant vesicular stomatitis virus vector vaccine against Nipah virus disease

IntroductionImmune correlates of protection afforded by PHV02, a recombinant vesicular stomatitis (rVSV) vector vaccine against Nipah virus (NiV) disease, were investigated in the African green monkey (AGM) model. Neutralizing antibody to NiV has been proposed as the principal mediator of protection against future NiV infection.MethodsTwo approaches were used to determine the correlation between neutralizing antibody levels and outcomes following a severe (1,000 median lethal doses) intranasal/intratracheal (IN/IT) challenge with NiV (Bangladesh): (1) reduction in vaccine dose given 28 days before challenge and (2) challenge during the early phase of the antibody response to the vaccine.ResultsReduction in vaccine dose to very low levels led to primary vaccine failure rather than a sub-protective level of antibody. All AGMs vaccinated with the nominal clinical dose (2 × 107 pfu) at 21, 14, or 7 days before challenge survived. AGMs vaccinated at 21 days before challenge had neutralizing antibodies (geometric mean titer, 71.3). AGMs vaccinated at 7 or 14 days before challenge had either undetectable or low neutralizing antibody titers pre-challenge but had a rapid rise in titers after challenge that abrogated the NiV infection. A simple logistic regression model of the combined studies was used, in which the sole explanatory variable was pre-challenge neutralizing antibody titers. For a pre-challenge titer of 1:5, the predicted survival probability is 100%. The majority of animals with pre-challenge neutralizing titer of ≥1:20 were protected against pulmonary infiltrates on thoracic radiograms, and a majority of those with titers ≥1:40 were protected against clinical signs of illness and against a ≥fourfold antibody increase following challenge (indicating sterile immunity). Controls receiving rVSV-Ebola vaccine rapidly succumbed to NiV challenge, eliminating the innate immunity stimulated by the rVSV vector as a contributor to survival in monkeys challenged as early as 7 days after vaccination.Discussion and conclusionIt was concluded that PHV02 vaccine elicited a rapid onset of protection and that any detectable level of neutralizing antibody was a functional immune correlate of survival

Heterogeneous economic returns to higher education: evidence from Italy

This paper uses official Italian micro data and different methods to estimate, in the framework of potential outcomes, the marginal return to college education allowing for heterogeneous returns and for self-selection into higher education. Specifically, the paper is focused on the estimation of heterogeneity of average treatment effect (ATE) on a cohort of college and high school graduates using the 2008 survey on household, income and wealth of the Bank of Italy. Methodologically, this study was carried out by using both propensity-score-based (PS-based) methods and a new approach based on marginal treatment effects (MTE), recently proposed by Heckman and his associates as a useful strategy when the ignorability assumption may be violated. In the PS-based approach, heterogeneous treatment effects are estimated in three different manners: the traditional stratification approach (propensity score strata), the regression adjustment within propensity score strata and, finally, a non-parametric smoothing approach. In the MTE approach, the treatment effect heterogeneity across individuals is estimated in a parametric as well as a semi-parametric strategy. Our empirical analysis shows that the estimated heterogeneity is substantial: following MTE based results (quite representative of other methods) the return to college graduation for a randomly selected individual varies from as high as 20 % (for persons who would add one fifth of wage from graduating college) to as low as 1222 % (for persons who would lose from college graduation), suggesting that returns are higher for individuals more likely to attend college. Furthermore, the results of different methods show very low (point) estimates of ATE: average college returns vary from 3.5 % by the PS-smoothing method to 1.8 % by the parametric MTE method, which also leads a greater treatment effect on treated (5.5 %), a moderate, but significant sorting gain and a negligible selection bias

Estimation of educational returns using university and labour market administrative archives

This study estimates the rate of return to education for University of Milan (Italy) graduates who were active in the labour market during the period 2003-05, using official administrative data (University archives, Regional Labour market archive and Italian National Internal Revenue Service archive). The rate of return is measured in terms of differences in wage rates associated with differences in education. Both the \u2018years of schooling completed\u2019 and the \u2018highest qualification obtained\u2019 dimensions of education are considered. Methodologically, we propose a longitudinal extension of the Correlated Random Coefficient Model that, in contrast to alternative approaches for estimating educational returns, permits simultaneous evaluation of education effects on the earnings of graduates in both a cross-sectional (income differences between years or levels of education in 2005), and in a longitudinal framework (differences in income growth rates during the period 2003-05, between years or levels of education). Furthermore, the problem of self-selection (non-randomness of income earners), as well as education endogeneity bias, is taken into account. Empirical results, based on three institutional administrative archives, demonstrate that workers sort themselves into higher paying work experiences and income growth trajectories, while also providing strong evidence for a positive ability bias. Secondly, cross-section education returns confirm that graduates receive an income advantage in proportion to the educational level achieved, whereas longitudinal returns do not confirm this finding