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Objective: To determine the long‐term impact of prior SARS‐CoV‐2 infection on immune responses after COVID‐19 vaccination. Methods: Using longitudinally collected blood samples from the COMMUNITY study, we determined binding (WHO BAU mL−1) and neutralising antibody titres against ten SARS‐CoV‐2 variants over 7 months following BNT162b2 in SARS‐CoV‐2‐recovered (n = 118) and SARS‐CoV‐2‐naïve (n = 289) healthcare workers with confirmed prior SARS‐CoV‐2 infection. A smaller group with (n = 47) and without (n = 60) confirmed prior SARS‐CoV‐2 infection receiving ChAdOx1 nCoV‐19 was followed for 3 months. SARS‐CoV‐2‐specific memory T‐cell responses were investigated in a subset of SARS‐CoV‐2‐naïve and SARS‐CoV‐2‐recovered vaccinees. Results: Vaccination with both vaccine platforms resulted in substantially enhanced T‐cell responses, anti‐spike IgG responses and neutralising antibodies effective against ten SARS‐CoV‐2 variants in SARS‐CoV‐2‐recovered participants as compared to SARS‐CoV‐2‐naïve participants. The enhanced immune responses sustained over 7 months following vaccination. Conclusion: These findings imply that prior SARS‐CoV‐2 infection should be taken into consideration when planning booster doses and design of current and future COVID‐19 vaccine programmes. [ABSTRACT FROM AUTHOR]

Tick-borne encephalitis virus (TBEV) is a flavivirus that is transferred to humans by infected ticks. The virus causes tick-borne encephalitis, a severe infection of the CNS with a high risk for long-lasting sequelae. Currently, no treatment exists for the disease. Understanding the cellular immune response to this infection is important to gain further understanding into the pathogenesis, treatment, and prevention of the disease. NK cells are known to participate in the control of viral infections. We performed a longitudinal analysis of the human NK cell response to TBEV infection in a cohort of infected individuals from the onset of severe clinical symptoms to the convalescence phase. NK cell activation, as measured by expression of Ki67, was apparent at the time of hospitalization. By 3 wk after hospitalization, it decreased to levels seen in healthy controls. Concomitant with the increase in NK cell activation, augmented levels of IL-12, IL-15, IL-18, IFN-y, and TNF were detected in patient plasma. This TBEV-induced NK cell activation was restricted predominantly to differentiated CD57+CD56dim NK cells. Functionally, CD56dim NK cells responded poorly to target cells at the time of hospitalization, but they recovered functional capacity to control levels during the convalescent phase. In contrast, the responsiveness of NK cells to cytokine stimulation remained intact throughout the disease. These findings demonstrate that NK cells respond to TBEV infection with characteristics that are distinct from those of other human viral infections and provide insights into the NK cell response to clinical TBEV infection. [ABSTRACT FROM AUTHOR]

HIV-1 disease progression is associated with persistent immune activation. However, the nature of this association is incompletely understood. Here, we investigated immune activation in the CD4 T cell compartment of chronically HIV-1 infected individuals from Rakai, Uganda. Levels of CD4 T cell activation, assessed as co-expression of PD-1, CD38 and HLADR, correlated directly to viral load and inversely to CD4 count. Deeper characterization of these cells indicated an effector memory phenotype with relatively frequent expression of Ki67 despite their PD-1 expression, and levels of these cells were inversely associated with FoxP3+ regulatory T cells. We therefore use the term deregulated effector memory (DEM) cells to describe them. CD4 T cells with a DEM phenotype could be generated by antigen stimulation of recall responses in vitro. Responses against HIV-1 and CMV antigens were enriched among the DEM CD4 T cells in patients, and the diverse Vb repertoire of DEM CD4 T cells suggested they include diverse antigen-specificities. Furthermore, the levels of DEM CD4 T cells correlated directly to soluble CD14 (sCD14) and IL-6, markers of innate immune activation, in plasma. The size of the activated DEM CD4 T cell subset was predictive of the rate of disease progression, whereas IL-6 was only weakly predictive and sCD14 was not predictive. Taken together, these results are consistent with a model where systemic innate immune activation and chronic antigen stimulation of adaptive T cell responses both play important roles in driving pathological CD4 T cell immune activation in HIV-1 disease. [ABSTRACT FROM AUTHOR]