Infection and vaccine induced Spike antibody responses against SARS-CoV-2 Variants of concern in immune naïve children and adults (preprint)

A more efficient and effective adaptive humoral immune response has been proposed as the basis of the usually favourable outcome of paediatric COVID-19. The breadth of virus and vaccine immunogenicity towards the ever-mutating Spike protein amongst variants of concern (VOC) have not yet been compared between children and adults. We utilized molecular cloning and sensitive antibody detection against conformational Spike by flow cytometry to assess Spike antibodies and delineate the immunogenic region in immune naïve children and adults vaccinated by BNT162b2 and ChAdOx1, and naturally infected with Early Clade, Delta, and Omicron variants. Patient sera were analysed against SARS-CoV-2 Spike antigens including naturally occurring VOCs Alpha, Beta, Gamma, Delta, Omicron BA.1, BA.2, and BA.5 variants of interest Epsilon, Kappa, Eta, D.2, and artificial Spike mutants. There was no notable difference between breadth and longevity of antibody responses generated against VOCs in children and adults. Vaccinated individuals displayed similar immunoreactivity profiles across variants to naturally infected individuals. Delta-infected patients had an enhanced immunogenicity toward Delta and some VOCs compared to patients infected by Early Clade SARS-CoV-2. Although Omicron BA.1, BA.2, and BA.5 antibody levels were increased after Omicron infection in both children and adults, immunogenicity against Omicron subvariants was reduced. This decrease was observed across VOC infection, immunization, and age groups. Selected epistatically combined mutations led to an increase of immunogenicity in artificial Spikes, but were unable to compensate overall within Omicron. Our results reveal important molecular features central to the generation of high antibody titers and broad immunoreactivity that should be considered in future vaccine design and global serosurveillance.

Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19 (preprint)

Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV-2-specific naive T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. More naive interferon-activated CD4+ T cells were recruited into the memory compartment and recovery was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.

Effects of 12 weeks of Multi-nutrient supplementation on the Immune and Musculoskeletal systems of Older Adults in Aged-Care (The Pomerium Study): Protocol for a Randomised Controlled Trial (preprint)

Introduction: Immunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with Sars-Cov2, which disproportionately impact older adults, particularly those in residential aged care facilities. Inadequate nutrient intake associated with impaired immunity, respiratory and muscle function are likely to augment the effects of immunosenescence. In this study, we test whether the effects of inadequate nutrition can be reversed by multi-nutrient supplementation, consequently enhancing vaccine responses, reducing the risk of viral infections, and improving respiratory and muscle function. Methods and analysis: The Pomerium Study is a 12-week, single-blinded, randomised, placebo-controlled trial testing the effects of two daily servings of an oral multi-nutrient supplement (330 kcal, 20g protein, 1.2g CaHMB, 449mg calcium, 520IU vitamin D3, and 25 vitamins and minerals) on the immune system and muscle and respiratory function of older adults in aged-care in Melbourne, Australia. 160 older adults ([≥]75 years old) will be recruited from aged-care facilities and randomised to treatment (multi-nutrient supplement) or control (usual care). Primary outcome is the change in T-cell subsets CD8+ and CD28null counts at 4 and 12 weeks post-intervention. Secondary outcomes measured at baseline and after 12 weeks post-intervention are multiple markers of immunosenescence, body composition (bioimpedance), handgrip strength (dynamometer), physical function (short physical performance battery), respiratory function (spirometry), and quality of life (EQ-5D-3L). Incidence and complications of COVID-19 and/or viral infections (i.e., hospitalisation, complications, or death) will be recorded throughout the trial. Discussion: If the Pomerium Study demonstrates efficacy and safety of a multi-nutrient supplement on immune, muscle and respiratory function, it may be suitable as a strategy to reduce the adverse outcomes from seasonal influenza and viral infections such as COVID-19 in older adults in aged-care.