Immunogenicity of COVID-19 vaccines in patients with follicular lymphoma receiving frontline chemoimmunotherapy.

Immune responses to primary COVID-19 vaccination were investigated in 58 patients with follicular lymphoma (FL) as part of the PETReA trial of frontline therapy (EudraCT 2016-004010-10). COVID-19 vaccines (BNT162b2 or ChAdOx1) were administered before, during or after cytoreductive treatment comprising rituximab (depletes B cells) and either bendamustine (depletes CD4+ T cells) or cyclophosphamide-based chemotherapy. Blood samples obtained after vaccine doses 1 and 2 (V1, V2) were analysed for antibodies and T cells reactive to the SARS-CoV-2 spike protein using the Abbott Architect and interferon-gamma ELISpot assays respectively. Compared to 149 healthy controls, patients with FL exhibited lower antibody but preserved T-cell responses. Within the FL cohort, multivariable analysis identified low pre-treatment serum IgA levels and V2 administration during induction or maintenance treatment as independent determinants of lower antibody and higher T-cell responses, and bendamustine and high/intermediate FLIPI-2 score as additional determinants of a lower antibody response. Several clinical scenarios were identified where dichotomous immune responses were estimated with >95% confidence based on combinations of predictive variables. In conclusion, the immunogenicity of COVID-19 vaccines in FL patients is influenced by multiple disease- and treatment-related factors, among which B-cell depletion showed differential effects on antibody and T-cell responses.

Links between the three-dimensional movements of whale sharks (Rhincodon typus) and the bio-physical environment off a coral reef.

BACKGROUND: Measuring coastal-pelagic prey fields at scales relevant to the movements of marine predators is challenging due to the dynamic and ephemeral nature of these environments. Whale sharks (Rhincodon typus) are thought to aggregate in nearshore tropical waters due to seasonally enhanced foraging opportunities. This implies that the three-dimensional movements of these animals may be associated with bio-physical properties that enhance prey availability. To date, few studies have tested this hypothesis. METHODS: Here, we conducted ship-based acoustic surveys, net tows and water column profiling (salinity, temperature, chlorophyll fluorescence) to determine the volumetric density, distribution and community composition of mesozooplankton (predominantly euphausiids and copepods) and oceanographic properties of the water column in the vicinity of whale sharks that were tracked simultaneously using satellite-linked tags at Ningaloo Reef, Western Australia. Generalised linear mixed effect models were used to explore relationships between the 3-dimensional movement behaviours of tracked sharks and surrounding prey fields at a spatial scale of ~ 1 km. RESULTS: We identified prey density as a significant driver of horizontal space use, with sharks occupying areas along the reef edge where densities were highest. These areas were characterised by complex bathymetry such as reef gutters and pinnacles. Temperature and salinity profiles revealed a well-mixed water column above the height of the bathymetry (top 40 m of the water column). Regions of stronger stratification were associated with reef gutters and pinnacles that concentrated prey near the seabed, and entrained productivity at local scales (~ 1 km). We found no quantitative relationship between the depth use of sharks and vertical distributions of horizontally averaged prey density. Whale sharks repeatedly dove to depths where spatially averaged prey concentration was highest but did not extend the time spent at these depth layers. CONCLUSIONS: Our work reveals previously unrecognized complexity in interactions between whale sharks and their zooplankton prey.