Early induction of anti-Spike binding antibodies and T cells confer protection against COVID-19 in children during an Omicron wave (preprint)

For improved safety, children are vaccinated with a lower dose and extended interval for mRNA COVID-19 vaccines; however, whether there is protection before dose 2 is unknown. We recruited 113 children receiving BNT162b2 primary vaccination during an Omicron wave. After dose 1, 96% had detectable anti-Spike(S) IgG and 100% had S-reactive T cells; those with both had a lower risk of symptomatic infection compared to those with undetectable anti-S IgG [RR 0.19 (95% CI; 0.06, 0.59)]. This suggests that dosing can be extended without risk of insufficient early protection.

Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine (preprint)

Remarkable potency has been demonstrated for mRNA vaccines in reducing the global burden of the ongoing COVID-19 pandemic. This vaccine platform has been extended to encode an alphavirus replicase that self-amplifies the full length mRNA and SARS-CoV-2 spike (S) transgene (self-amplifying mRNA or sa mRNA). However, early phase clinical trials of sa-mRNA COVID-19 vaccine candidates have questioned the potential of this platform to develop potent vaccines. We examined the immune gene response to a candidate sa-mRNA vaccine against COVID-19, and compared our findings to the host response to other forms of vaccines. In blood samples from healthy volunteers that participated in a phase I/II clinical trial, greater induction of transcripts involved in Toll-like receptor (TLR) signalling, antigen presentation and complement activation at 1 day post-vaccination was associated with higher anti-S antibody titers. Conversely, transcripts involved in T-cell maturation at day 7 post-vaccination informed the magnitude of eventual anti-S T-cell responses. The transcriptomic signature for ARCT-021 vaccination strongly correlated with live viral vector vaccines, adjuvanted vaccines and BNT162b2. Correlation with live attenuated vaccines was weaker. Our findings suggest the potential for sa-mRNA to be further developed to be among the most potent forms of vaccines in our arsenal to prevent infectious diseases.

Signatures of mast cell activation are associated with severe COVID-19 (preprint)

Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in severely ill patients and the pathophysiology of disease is thought to be immune-mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens, often promoting inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and non-human primates. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype. MC activation in humans was confirmed, through detection of the MC-specific protease, chymase, levels of which were significantly correlated with disease severity. These results support the association of MC activation with severe COVID-19, suggesting potential strategies for intervention.