BackgroundAllergen-specific immunotherapy represents the only disease-modifying treatment for allergic diseases. We and others have previously demonstrated that intralymphatic immunotherapy (ILIT), a less time-consuming alternative to conventional subcutaneous immunotherapy (SCIT), is safe and effective. However, this has recently been disputed. The aim of this study was therefore to expand our previous trial, further assessing the safety and efficacy of ILIT.MethodsThirty-six patients with pollen-induced rhinoconjunctivitis were randomised to receive three intralymphatic inguinal injections of active allergen (1000 SQ-U birch- or grass-pollen) or placebo. Clinical effects, safety and circulating immunological markers were assessed before, 4 weeks after treatment and at the end of the consecutive pollen season.ResultsNo moderate or severe reactions were recorded following ILIT. Patients receiving active ILIT experienced a significant improvement in self-recorded seasonal allergic symptoms, as compared to placebo (p = 0.05). In a subgroup of these patients (“improved”), a reduction in nasal symptoms following nasal allergen provocation was also demonstrated. No changes in total IgE or IgG4 were found. However, the affinity of allergen specific IgG4 following active treatment was significantly increased, as compared to non-improved patients (p = 0.04). This could be correlated with clinical improvement, on an individual level.ConclusionsThis double-blinded placebo-controlled study confirms that ILIT is a safe and effective treatment for pollen-induced rhinoconjunctivitis, markedly reducing seasonal allergic symptoms.Trial registrationEudraCT: 2009-016815-39Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0324-9) contains supplementary material, which is available to authorized users.

Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization correlate with the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.

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Dutta and co-workers suggest in a recent letter (1) that the SARS-CoV-2 nucleoprotein (N) might be a good vaccine target.…

Antibodies play a central role in the immune defense against SARS-CoV-2. Emerging evidence has shown that nonneutralizing antibodies are important for immune defense through Fc-mediated effector functions. Antibody subclass is known to affect downstream Fc function. However, whether the antibody subclass plays a role in anti-SARS-CoV-2 immunity remains unclear. Here, we subclass-switched eight human IgG1 anti-spike monoclonal antibodies (mAbs) to the IgG3 subclass by exchanging their constant domains. The IgG3 mAbs exhibited altered avidities to the spike protein and more potent Fc-mediated phagocytosis and complement activation than their IgG1 counterparts. Moreover, combining mAbs into oligoclonal cocktails led to enhanced Fc- and complement receptor-mediated phagocytosis, superior to even the most potent single IgG3 mAb when compared at equivalent concentrations. Finally, in an in vivo model, we show that opsonic mAbs of both subclasses can be protective against a SARS-CoV-2 infection, despite the antibodies being nonneutralizing. Our results suggest that opsonic IgG3 oligoclonal cocktails are a promising idea to explore for therapy against SARS-CoV-2, its emerging variants, and potentially other viruses.

It is well-established that bacterial and viral infections have an exacerbating effect on allergic asthma, particularly aggravating respiratory symptoms, such as airway hyperresponsiveness (AHR). The mechanism by which these infections alter AHR is unclear, but some studies suggest that Toll-like receptors (TLRs) play a role. In this study, we investigated the impact of TLR3 and TLR4 ligands on AHR and airway inflammation in a model of pre-established allergic inflammation. Female BALB/c mice were sensitised and challenged intranasally (i.n.) with either PBS or ovalbumin (OVA) and subsequently i.n. challenged with poly (I:C) (TLR3) or LPS (TLR4) for four consecutive days. The response to methacholine was measured in vivo; cellular and inflammatory mediators were measured in blood, lung tissue and broncheoalveolar lavage fluid (BALF). OVA challenge resulted in an increase in AHR to methacholine, as well as increased airway eosinophilia and TH2 cytokine production. Subsequent challenge with TLR agonists resulted in a significant increase in AHR, but decreased TLR-specific cellular inflammation and production of immune mediators. Particularly evident was a decline in LPS-induced neutrophilia and neutrophil-associated cytokines following LPS and poly (I:C) treatment. The present data indicates that TLRs may play a pivotal role in AHR in response to microbial infection in allergic lung inflammation. These data also demonstrate that aggravated AHR occurs in the absence of an exacerbation in airway inflammation and that allergic inflammation impedes a subsequent inflammatory response to TLRs. These results may parallel clinical signs of microbial asthma exacerbation, including an extended duration of illness and increased respiratory symptoms.

This highlights a novel role for sensory neuropeptides as acute and local mediators of pathogen-driven inflammation, rapidly priming innate immune defenses in the airway.

Iron stores, as measured by serum ferritin, are small in young men studied at the end of their growth spurt. However, iron deficiency is rare. Therefore, the present study has not been able to confirm the high prevalence of iron deficiency recently reported. A prevalence of genetic haemochromatosis of 0.4%, confirms earlier findings and would mean that 12.6% of the population are heterozygotic carriers of the iron-loading genes. These findings give no support for a proposed, more effective iron-enrichment of food. It is not needed and can be harmful.