SARS-CoV-2 infected children form early immune memory responses dominated by nucleocapsid-specific CD8+ T cells and antibodies.

This is the third year of the SARS-CoV-2 pandemic, and yet most children remain unvaccinated. COVID-19 in children manifests as mostly mild or asymptomatic, however high viral titers and strong cellular and humoral responses are observed upon acute infection. It is still unclear how long these responses persist, and if they can protect from re-infection and/or disease severity. Here, we analyzed immune memory responses in a cohort of children and adults with COVID-19. Important differences between children and adults are evident in kinetics and profile of memory responses. Children develop early N-specific cytotoxic T cell responses, that rapidly expand and dominate their immune memory to the virus. Children's anti-N, but not anti-S, antibody titers increase over time. Neutralization titers correlate with N-specific antibodies and CD8+T cells. However, antibodies generated by infection do not efficiently cross-neutralize variants Gamma or Delta. Our results indicate that mechanisms that protect from disease severity are possibly different from those that protect from reinfection, bringing novel insights for pediatric vaccine design. They also underline the importance of vaccination in children, who remain at risk for COVID-19 despite having been previously infected.

Development and immunobiological evaluation of nanoparticles containing an immunodominant epitope of herpes simplex virus.

Herpes simplex virus (HSV) 1 and 2 are viruses that infect individuals worldwide and for which there is no cure or vaccine available. The protective response against herpes is mostly mediated by CD8 T lymphocytes that respond to the immunodominant SSIEFARL epitope. However, there are some obstacles concerning the use of free SSIEFARL for vaccine or immunotherapy. The aim of this study was to evaluate the feasibility of nanoencapsulation of SSIEFARL and its immunostimulatory properties. Nano/SSIEFARL was produced by interfacial polymerization in methylmetacrylate, and the physico-chemical properties, morphology and immunobiological parameters were evaluated. To evaluate the ex vivo capacity of Nano/SSIEFARL, we used splenocytes from HSV-1-infected mice to enhance the frequency of SSIEFARL-specific CD8 T lymphocytes. The results indicate that Nano/SSIEFARL has a spherical shape, an average diameter of 352 ± 22 nm, the PDI was 0.361 ± 0.009 and is negatively charged (-26.30 ± 35). The stability at 4°C was 28 days. Also, Nano/SSIEFARL is not toxic for cells at low concentrations in vitro and it is taken up by JAWS II dendritic cells. No histopathological changes were observed in kidneys, liver and lymph nodes of animals treated with Nano/SSIEFARL. Nan/SSIEFARL increased the production of IL-1ß, TNF-α and IL-12 by the dendritic cells. Finally, Nano/SSIEFARL expanded the frequency of SSIEFARL-specific CD8+T lymphocytes at the same rate as free SSIEFARL. In conclusion all data together indicate that SSIEFARL is suitable for nanoencapsulation, and the system produced presents some immunoadjuvant properties that can be used to improve the immune response against herpes.

RvD1 treatment during primary infection modulates memory response increasing viral load during respiratory viral reinfection.

Resolvin D1 (RvD1), which is biosynthesized from essential long-chain fatty acids, is involved in anti-inflammatory activity and modulation of T cell response. Memory CD8+ T cells are important for controlling tumor growth and viral infections. Exacerbated inflammation has been described as impairing memory CD8+ T cell differentiation. This study aimed to verify the effects of RvD1 on memory CD8+ T cells in vitro and in vivo in a respiratory virus infection model. Peripheral blood mononuclear cells were treated at different time points with RvD1 and stimulated with anti-CD3/anti-CD28 antibodies. Pre-treatment with RvD1 increases the expansion of memory CD8+ T cells. The IL-12 level, a cytokine described to control memory CD8+ T cells, was reduced with RvD1 pre-treatment. When the mTOR axis was inhibited, the IL-12 levels were restored. In a respiratory virus infection model, Balb/c mice were treated with RvD1 before infection or after 7 days after infection. RvD1 treatment after infection increased the frequency of memory CD8+ T cells in the lung expressing II4, II10, and Ifng. During reinfection, RvD1-treated and RSV-infected mice present a high viral load in the lung and lower antibody response in the serum. Our results show that RvD1 modulates the expansion and phenotype of memory CD8+ T cells but contributed to a non-protective response after RSV reinfection.

Pediatric COVID-19 patients in South Brazil show abundant viral mRNA and strong specific anti-viral responses.

COVID-19 manifests as a milder disease in children than adults, but the underlying mechanisms are not fully characterized. Here we assess the difference in cellular or humoral immune responses of pediatric and adult COVID-19 patients to see if these factors contribute to the severity dichotomy. Children's non-specific immune profile is dominated by naive lymphocytes and HLA-DRhighCX3CR1low dendritic cells; meanwhile, children show strong specific antibody and T cell responses for viral structural proteins, with their T cell responses differing from adults by having weaker CD8+TNF+ T cells responses to S peptide pool but stronger responses to N and M peptide pools. Finally, viral mRNA is more abundant in pediatric patients. Our data thus support a scenario in which SARS-CoV-2 infected children contribute to transmission yet are less susceptible to COVID-19 symptoms due to strong and differential responses to the virus.