Search

New immune evasive variants of SARS‐CoV‐2 continue to emerge, potentially causing new waves of covid‐19 disease. Here, we evaluate levels of neutralizing antibodies against isolates of Omicron variants, including BQ.1.1 and XBB, in sera harvested 3–4 weeks after vaccination or breakthrough infections. In addition, we evaluate neutralizing antibodies in 32 sera from October 2022, to evaluate immunity in Norwegian donors prior to the winter season. Most serum samples harvested in October 2022 had low levels of neutralizing antibodies against BQ.1.1 and especially XBB, explaining why these variants and their descendants have dominated in Norway during the 2022 and 2023 winter season. [ABSTRACT FROM AUTHOR]

Targeting antigens to cross-presenting dendritic cells (DCs) is a promising method for enhancing CD8+ T-cell responses. However, expression patterns of surface receptors often vary between species, making it difficult to relate observations in mice to other animals. Recent studies have indicated that the chemokine receptor Xcr1 is selectively expressed on cross-presenting murine CD8α+ DCs, and that the expression is conserved on homologous DC subsets in humans (CD141+ DCs), sheep (CD26+ DCs), and macaques (CADM1+ DCs). We therefore tested if targeting antigens to Xcr1 on cross-presenting DCs using antigen fused to Xcl1, the only known ligand for Xcr1, could enhance immune responses. Bivalent Xcl1 fused to model antigens specifically bound CD8α+ DCs and increased proliferation of antigen-specific T cells. DNA vaccines encoding dimeric Xcl1-hemagglutinin (HA) fusion proteins induced cytotoxic CD8+ T-cell responses, and mediated full protection against a lethal challenge with influenza A virus. In addition to enhanced CD8+ T-cell responses, targeting of antigen to Xcr1 induced CD4+ Th1 responses and highly selective production of IgG2a antibodies. In conclusion, targeting of dimeric fusion vaccine molecules to CD8α+ DCs using Xcl1 represents a novel and promising method for induction of protective CD8+ T-cell responses. [ABSTRACT FROM AUTHOR]

Immunocompromised patients often fail to raise protective vaccine-induced immunity against the global emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Although monoclonal antibodies have been authorized for clinical use, most have lost their ability to potently neutralize the evolving Omicron subvariants. Thus, there is an urgent need for treatment strategies that can provide protection against these and emerging SARS-CoV-2 variants to prevent the development of severe coronavirus disease 2019. Here, we report on the design and characterization of a long-acting viral entry-blocking angiotensin-converting enzyme 2 (ACE2) dimeric fusion molecule. Specifically, a soluble truncated human dimeric ACE2 variant, engineered for improved binding to the receptor-binding domain of SARS-CoV-2, was fused with human albumin tailored for favorable engagement of the neonatal fragment crystallizable receptor (FcRn), which resulted in enhanced plasma half-life and allowed for needle-free transmucosal delivery upon nasal administration in human FcRn-expressing transgenic mice. Importantly, the dimeric ACE2-fused albumin demonstrated potent neutralization of SARS-CoV-2 immune escape variants., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

Targeting antigens to cross-presenting dendritic cells (DCs) is a promising method for enhancing CD8(+) T-cell responses. However, expression patterns of surface receptors often vary between species, making it difficult to relate observations in mice to other animals. Recent studies have indicated that the chemokine receptor Xcr1 is selectively expressed on cross-presenting murine CD8α(+) DCs, and that the expression is conserved on homologous DC subsets in humans (CD141(+) DCs), sheep (CD26(+) DCs), and macaques (CADM1(+) DCs). We therefore tested if targeting antigens to Xcr1 on cross-presenting DCs using antigen fused to Xcl1, the only known ligand for Xcr1, could enhance immune responses. Bivalent Xcl1 fused to model antigens specifically bound CD8α(+) DCs and increased proliferation of antigen-specific T cells. DNA vaccines encoding dimeric Xcl1-hemagglutinin (HA) fusion proteins induced cytotoxic CD8(+) T-cell responses, and mediated full protection against a lethal challenge with influenza A virus. In addition to enhanced CD8(+) T-cell responses, targeting of antigen to Xcr1 induced CD4(+) Th1 responses and highly selective production of IgG2a antibodies. In conclusion, targeting of dimeric fusion vaccine molecules to CD8α(+) DCs using Xcl1 represents a novel and promising method for induction of protective CD8(+) T-cell responses., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)