The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to stimulate pre-existing memory T cells established by seasonal human influenza A infection that could cross-react with H5N1 by targeting highly conserved internal proteins. To determine how common cross-reactive T cells are, we performed a comprehensive ex vivo analysis of cross-reactive CD4 + and CD8 +

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Streptococcus pneumoniae (pneumococcus) and respiratory syncytial virus (RSV) are the leading causes of respiratory infections amongst children <5 years of age. Co-infection with these pathogens is common during early life and often associated with increased disease severity. Epidemiological studies have shown that low levels of Vitamin D 3 (VitD 3) are associated with increased susceptibility to respiratory pathogens. However, the role of VitD 3 in the context of pneumococcal and RSV exposure are poorly understood. We found that VitD 3 significantly reduced Th17 cell expression and IL-17A and IL-22 secretion in peripheral blood mononuclear cells (PBMCs) when stimulated with a pneumococcal whole cell antigen (WCA). Levels of IFN-γ were also decreased whilst IL-10 and IL-1β were increased. Effects of VitD 3 on innate responses following RSV stimulation was limited, only reducing IL-6. VitD 3 also reduced the number of TLR2+CD14+ monocytes, whilst increasing TLR7+CD14+ monocytes and TLR4+CD56+ NK cells. In WCA-stimulated PBMCs, VitD 3 increased IL-1β levels but reduced TLR2+CD14+ monocytes. For pneumococcal WCA-RSV co-stimulation, VitD 3 only had a limited effect, mainly through increased IL-1β and RANTES as well as TLR4+CD56+ NK cells. Our results suggest that VitD 3 can modulate the inflammatory response to pneumococci but has limited effects during viral or bacterial-viral exposure. This is the first study to examine the effects of VitD 3 in the context of pneumococcal-RSV co-stimulation, with important implications on the potential role of VitD 3 in the control of excessive inflammatory responses during pneumococcal and RSV infections.

Respiratory syncytial virus (RSV) is the most common viral pathogen associated with acute lower respiratory tract infection (LRTI) in children under 5 years of age. Severe RSV disease is associated with the development of chronic respiratory complications such as recurrent wheezing and asthma. A common risk factor for developing severe RSV disease is premature gestation and this is largely due to an immature innate immune system. This increases susceptibility to RSV since the innate immune system is less able to protect against pathogens at a time when adaptive immunity has not fully developed. This review focuses on comparing different aspects of innate immunity between preterm and term infants to better understand why preterm infants are more susceptible to severe RSV disease. Identifying early life innate immune biomarkers associated with the development of severe RSV disease, and understanding how these compare between preterm and term infants, remains a critically important question that would aid the development of interventions to reduce the burden of disease in this vulnerable population.