humoral innate immunity pattern recognition molecules

Pan-SARS neutralizing responses after third boost vaccination in non-human primate immunogenicity model

Pan-SARS neutralizing responses after third boost vaccination in non-human primate immunogenicity model

specially Beta and Delta, has raised concerns about the reduced protection from previous infection or vaccination based on the original Wuhan-Hu-1 (D614) virus. To identify promising regimens for inducing neutralizing titers towards new variants, we evaluated monovalent and bivalent mRNA vaccines either as primary vaccination or as a booster in nonhuman primates (NHPs). Two mRNA vaccines, D614-based MRT5500 and Beta-based MRT5500β, tested in sequential regimens or as a bivalent combination in naïve NHPs produced modest neutralizing titers to heterologous variants.

However, when mRNA vaccines were administered as a booster to pre-immune NHPs, we observed a robust increase in neutralizing titers with expanded breadth towards all tested variants, and notably SARS CoV-1. The breadth of the neutralizing response was independent of vaccine sequence or modality, as we further showed either MRT5500 or recombinant subunit Spike protein (with adjuvant) can serve as boosters to induce broadly neutralizing <em>antibodies</em> in the NHPs primed with MRT5500. The data support the notion that a third vaccination is key to boosting existing titers and improving the breadth of antibodies to address variants of concern, including those with an E484K mutation in the Receptor Binding Domain (RBD) (Beta, Gamma).

Seroprevalence of SARS-CoV-2 antibodies in blood donors during the third wave of infection in Campeche Mexico

Deciphering the contributions of neuroinflammation to neurodegeneration: lessons from antibody-mediated encephalitis and coronavirus disease 2019

Does neuroinflammation promote neurodegeneration? Does neurodegeneration promote neuroinflammation? Or, is the answer to both questions, yes? These questions have proven challenging to answer in patients with typical age-related neurodegenerative diseases in whom the onset of neuroinflammation and neurodegeneration are largely unknown. Patients recovering from diseases associated with abrupt-onset neuroinflammation, including rare forms of antibody mediated encephalitis (AME) and common complications of novel coronavirus disease 2019, provide a unique opportunity to untangle the relationship between neuroinflammation and neurodegeneration.

Persistent cognitive impairment is increasingly recognized in patients recovering from AME or COVID 19, yet the drivers of impairment remain largely unknown. Clinical observations, neuroimaging and biofluid biomarkers, and pathological studies imply a link between the severity of acute neuroinflammation, subsequent neurodegeneration, and disease-associated morbidity.