have formed a joint venture with shared ownership and governance of Baylor Genetics (BG), which performs clinical microarray analysis and clinical exome sequencing. JRL serves on the scientific advisory board of BG. JRL has stock ownership in 23andMe, is a paid consultant for Regeneron Pharmaceuticals, and is a coinventor on multiple US and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting (

BackgroundThe development of an effective AIDS vaccine has been a formidable task, but remains a critical necessity. The well conserved membrane-proximal external region (MPER) of the HIV-1 gp41 glycoprotein is one of the crucial targets for AIDS vaccine development, as it has the necessary attribute of being able to elicit antibodies capable of neutralizing diverse isolates of HIV.Methodology/Principle FindingsGuided by X-ray crystallography, molecular modeling, combinatorial chemistry, and powerful selection techniques, we designed and produced six combinatorial libraries of chimeric human rhinoviruses (HRV) displaying the MPER epitopes corresponding to mAbs 2F5, 4E10, and/or Z13e1, connected to an immunogenic surface loop of HRV via linkers of varying lengths and sequences. Not all libraries led to viable chimeric viruses with the desired sequences, but the combinatorial approach allowed us to examine large numbers of MPER-displaying chimeras. Among the chimeras were five that elicited antibodies capable of significantly neutralizing HIV-1 pseudoviruses from at least three subtypes, in one case leading to neutralization of 10 pseudoviruses from all six subtypes tested.ConclusionsOptimization of these chimeras or closely related chimeras could conceivably lead to useful components of an effective AIDS vaccine. While the MPER of HIV may not be immunodominant in natural infection by HIV-1, its presence in a vaccine cocktail could provide critical breadth of protection.

The United Kingdom (UK) government set a target of offering all adults 2 doses of vaccination against the novel pandemic coronavirus (SARS-CoV-2, COVID-19) by 19th July 2021. The success of this national immunisation programme is dependent on both patient engagement and efficacy of the host immune response. Information on these factors remains limited in the setting of primary and secondary immunodeficiency [1,2]. Here we report on vaccine uptake and responses in adults under care of the Immunodeficiency Centre for Wales (ICW) revealing heterogenous anti-SARS-CoV-2 spike IgG responses across common diagnostic immunodeficiency sub-groups. With continued community circulation of SARS-CoV-2 and rising case rates, serosurveillance of vulnerable patient groups facilitates prompt and rational access to precision therapies such as monoclonal anti-SARS-CoV-2 antibodies.

Aicardi-Goutières syndrome (AGS) is a rare hereditary early-onset encephalopathy. The syndrome was first described in 1984, and is characterised by upregulation of the type I interferon (IFN) pathway, which is involved in the host immune response against viral infections, including SARS-CoV-2. Whilst defects in type I IFN pathways have been described in association with severe coronavirus disease 2019 (COVID-19), less is known about the outcomes of upregulation. We describe an unusual case of generalised panniculitis as a post-COVID-19 phenomenon in a child with AGS. Our patient was initially managed with systemic steroid therapy, but due to relapse of symptoms on weaning, an alternative therapy was sought. In this case, a novel use of ruxolitinib, a JAK inhibitor, has resulted in lasting remission without complications. We discuss the probable protective role of IFN upregulation following COVID-19 infection in AGS and possible immunological mechanisms driving the panniculitis and therapeutic response in our case.

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