da Costa KAS, Del Rosario JMM, Ferrari M, Vishwanath S, Asbach B, Kinsley R, Wagner R, Heeney JL, Carnell GW, Temperton NJ.

Vaccines (Basel). 2022 Sep 14;10(9):1520. doi: 10.3390/vaccines10091520.

ABSTRACT

To better understand how inhibition of the influenza neuraminidase (NA) protein contributes to protection against influenza, we produced lentiviral vectors pseudotyped with an avian H11 hemagglutinin (HA) and the NA of all influenza A (N1-N9) subtypes and influenza B (B/Victoria and B/Yamagata). These NA viral pseudotypes (PV) possess stable NA activity and can be utilized as target antigens in in vitro assays to assess vaccine immunogenicity. Employing these NA PV, we developed an enzyme-linked lectin assay (pELLA) for routine serology to measure neuraminidase inhibition (NI) titers of reference antisera, monoclonal antibodies and post-vaccination sera with various influenza antigens. We also show that the pELLA is more sensitive than the commercially available NA-Fluor™ in detecting NA inhibition in these samples. Our studies may lead to establishing the protective NA titer that contributes to NA-based immunity. This will aid in the design of superior, longer lasting and more broadly protective vaccines that can be employed together with HA-targeted vaccines in a pre-pandemic approach.

PMID:36146598 | PMC:PMC9571397 | DOI:10.3390/vaccines10091520

Sigl C, Dietz H.

Biospektrum (Heidelb). 2022;28(2):165-167. doi: 10.1007/s12268-022-1729-2. Epub 2022 Mar 28.

ABSTRACT

The current pandemic has highlighted the need for new antiviral therapies, to respond to existing and emerging diseases transmitted by viral vectors. We developed a novel antiviral approach that is based on neutralizing viruses by trapping and encapsulation in artificial nano-shells. The surrounding shells prevent the interaction of viruses with host cells and thus interrupt an essential step in the lifecycle of most viruses.

PMID:35369111 | PMC:PMC8960677 | DOI:10.1007/s12268-022-1729-2

Staufer O, Gupta K, Hernandez Bücher JE, Kohler F, Sigl C, Singh G, Vasileiou K, Yagüe Relimpio A, Macher M, Fabritz S, Dietz H, Cavalcanti Adam EA, Schaffitzel C, Ruggieri A, Platzman I, Berger I, Spatz JP.

Nat Commun. 2022 Feb 14;13(1):868. doi: 10.1038/s41467-022-28446-x.

ABSTRACT

SARS-CoV-2 infection is a major global public health concern with incompletely understood pathogenesis. The SARS-CoV-2 spike (S) glycoprotein comprises a highly conserved free fatty acid binding pocket (FABP) with unknown function and evolutionary selection advantage^1,2. Deciphering FABP impact on COVID-19 progression is challenged by the heterogenous nature and large molecular variability of live virus. Here we create synthetic minimal virions (MiniVs) of wild-type and mutant SARS-CoV-2 with precise molecular composition and programmable complexity by bottom-up assembly. MiniV-based systematic assessment of S free fatty acid (FFA) binding reveals that FABP functions as an allosteric regulatory site enabling adaptation of SARS-CoV-2 immunogenicity to inflammation states via binding of pro-inflammatory FFAs. This is achieved by regulation of the S open-to-close equilibrium and the exposure of both, the receptor binding domain (RBD) and the SARS-CoV-2 RGD motif that is responsible for integrin co-receptor engagement. We find that the FDA-approved drugs vitamin K and dexamethasone modulate S-based cell binding in an FABP-like manner. In inflammatory FFA environments, neutralizing immunoglobulins from human convalescent COVID-19 donors lose neutralization activity. Empowered by our MiniV technology, we suggest a conserved mechanism by which SARS-CoV-2 dynamically couples its immunogenicity to the host immune response.

PMID:35165285 | PMC:PMC8844029 | DOI:10.1038/s41467-022-28446-x