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Whether class-size reductions improve student learning outcomes is an important policy question for India. This paper investigates the issue using a credible identification strategy to address the endogeneity of class size. Pupil fixed effects combined with value-added estimation show no significant relationship between class size and student achievement, which suggests that under current teaching practices, there is no learning gain from reducing class size. If these findings, based on a small sample in one city, hold true for the entire country, they have important policy implications. When generalized, our findings suggest that India experienced a value-subtraction from spending on reducing class sizes, and that the US$3.6 billion it spends annually on the salaries of the 0.4 million new teachers appointed between 2010 and 2017 is wasteful spending rather than an investment in improving learning. These findings imply that India could save US$19.4 billion per annum by increasing PTR to 40, without any reduction in pupil learning. [ABSTRACT FROM AUTHOR]

Most modern research into the immune effects of breast milk has focused on the impacts of immunoglobulin or oligosaccharide content. However, immediately prior to parturition, the cell populations of breast milk become selectively enriched for CD8+ T cells of an effector memory subtype. Despite this observation that the cellular content of breast milk contains a distinct leukocyte population when compared to peripheral blood, the physiologic role of these CD8+ effector memory cells is unknown. Research encompassing animal models and humans has demonstrated that leukocytes are capable of transferring antigen‐specific immunity even when lysed, dialyzed to enrich for fractions less than 10 kDa, and orally administered. Our previous work built upon these reports to elucidate several aspects of this dialyzable leukocyte extract (DLE) activity: only DLE from T effector memory CD8+ cells was capable of transferring antigen‐specific immunity; the DLE activity was TCRβ dependent; dendritic cells (DCs) were the cellular target of DLE; and DLE enhanced immune activity in epithelial challenge models via induction of IL‐6 from DCs. Herein, we reveal that breast milk dialysate activates similar cytokine and genetic pathways as DLE taken from peripheral blood and murine spleens through TCRβ‐ and CD8‐dependent mechanisms. These findings suggest that the CD8+ memory T cells enriched in breast milk, even after potential lysis in the infant gut, may represent a mechanism for passive transfer of cellular immunity from mother to child. [ABSTRACT FROM AUTHOR]

Multiple candidate vaccines against Staphylococcus aureus infections have failed in clinical trials. Analysis of a recent prematurely halted vaccine trial revealed increased mortality rates among vaccine recipients in whom postsurgical S. aureus infection developed, emphasizing the potential for induction of detrimental immune responses and the need to better understand the requirements for protective immunity against S. aureus. These failures of single-antigen vaccines have prompted ongoing development of multicomponent vaccines to target the multitude of S. aureus virulence factors. In the current study, we used lethally irradiated S. aureus as a model multicomponent vaccine and showed that vaccination of mice decreased survival in a bacteremia challenge model. These deleterious effects were due to a CD4 T-cell-dependent interferon γ response and could be prevented by inhibiting development of this response during vaccination. Our results identify the potential for vaccination to induce pathological immune responses, and they have implications for recent vaccine failures and the design of future staphylococcal vaccines. [ABSTRACT FROM AUTHOR]

Author response. [ABSTRACT FROM AUTHOR]

Spores of Bacillus subtilis are encased in a protein coat composed of ∼80 different proteins. Recently, we reconstituted the basement layer of the coat, composed of two structural proteins (SpoVM and SpoIVA) around spore-sized silica beads encased in a lipid bilayer, to create synthetic spore-like particles termed 'SSHELs'. We demonstrated that SSHELs could display thousands of copies of proteins and small molecules of interest covalently linked to SpoIVA. In this study, we investigated the efficacy of SSHELs in delivering vaccines. We show that intramuscular vaccination of mice with undecorated one micron-diameter SSHELs elicited an antibody response against SpoIVA. We further demonstrate that SSHELs covalently modified with a catalytically inactivated staphylococcal alpha toxin variant (HlaH35L), without an adjuvant, resulted in improved protection against Staphylococcus aureus infection in a bacteremia model as compared to vaccination with the antigen alone. Although vaccination with either HlaH35L or HlaH35L conjugated to SSHELs similarly elicited the production of neutralizing antibodies to Hla, we found that a subset of memory T cells was differentially activated when the antigen was delivered on SSHELs. We propose that the particulate nature of SSHELs elicits a more robust immune response to the vaccine that results in superior protection against subsequent S. aureus infection. [ABSTRACT FROM AUTHOR]