Immune requirements for protective Th17 recall responses to Mycobacterium tuberculosis challenge.

Tuberculosis (TB) vaccine development has focused largely on targeting T helper type 1 (Th1) cells. However, despite inducing Th1 cells, the recombinant TB vaccine MVA85A failed to enhance protection against TB disease in humans. In recent years, Th17 cells have emerged as key players in vaccine-induced protection against TB. However, the exact cytokine and immune requirements that enable Th17-induced recall protection remain unclear. In this study, we have investigated the requirements for Th17 cell-induced recall protection against Mycobacterium tuberculosis (Mtb) challenge by utilizing a tractable adoptive transfer model in mice. We demonstrate that adoptive transfer of Mtb-specific Th17 cells into naive hosts, and upon Mtb challenge, results in Th17 recall responses that confer protection at levels similar to vaccination strategies. Importantly, although interleukin (IL)-23 is critical, IL-12 and IL-21 are dispensable for protective Th17 recall responses. Unexpectedly, we demonstrate that interferon-γ (IFN-γ) produced by adoptively transferred Th17 cells impairs long-lasting protective recall immunity against Mtb challenge. In contrast, CXCR5 expression is crucial for localization of Th17 cells near macrophages within well-formed B-cell follicles to mediate Mtb control. Thus, our data identify new immune characteristics that can be harnessed to improve Th17 recall responses for enhancing vaccine design against TB.

Improvement of BCG protective efficacy with a novel chimpanzee adenovirus and a modified vaccinia Ankara virus both expressing Ag85A.

A replication-deficient chimpanzee adenovirus expressing Ag85A (ChAdOx1.85A) was assessed, both alone and in combination with modified vaccinia Ankara also expressing Ag85A (MVA85A), for its immunogenicity and protective efficacy against a Mycobacterium tuberculosis (M.tb) challenge in mice. Naïve and BCG-primed mice were vaccinated or boosted with ChAdOx1.85A and MVA85A in different combinations. Although intranasally administered ChAdOx1.85A induced strong immune responses in the lungs, it failed to consistently protect against aerosol M.tb challenge. In contrast, ChAdOx1.85A followed by MVA85A administered either mucosally or systemically, induced strong immune responses and was able to improve the protective efficacy of BCG. This vaccination regime has consistently shown superior protection over BCG alone and should be evaluated further.

Dendritic cells as immune regulators: the mouse model.

Dendritic cells (DC) are central to the immune system because of their role in antigen presentation leading to either tolerance or immunity among cells of the adaptive immune response. It is becoming increasingly evident that DC show extensive plasticity in terms of their origin and function, giving rise to a number of subsets represented differentially in all lymphoid organs. This article considers the tolerogenic capacity of murine DC and draws a distinction between DC that induce tolerance in the immature state and immunity in an inflammatory context, and those that act as regulatory cells inducing immunosuppression in the presence of inflammation.

Comparison of axillary, rectal and tympanic temperature measurements in children admitted with malaria.

We compared axillary, rectal and tympanic temperatures in children admitted with severe malaria. The axillary temperatures were 0.74 degrees C (95% limits of agreement -0.85 to 2.33 degrees C) less than rectal temperatures and tympanic temperatures 0.42 degrees C (95% limits of agreement -0.16 to 2.44 degrees C) less than rectal temperatures. The difference was greater on admission than 24 hours later. These differences may be important in defining criteria for clinical syndromes.