Biology subjects

Radvak, P.

Publications and source records attributed to Radvak, P..

3 recordsLinked to original sources

bioRxiv2021

B.1.1.7 and B.1.351 variants are highly virulent in K18-ACE2 transgenic mice and show different pathogenic patterns from early SARS-CoV-2 strains

SARS-CoV-2 continues to circulate globally resulting in emergence of several variants of concern (VOC), including B.1.1.7 and B.1.351 that show increased transmissibility and enhanced resistance to antibody neutralization. In a K18-hACE2 transgenic mouse model, we demonstrate that Both B.1.1.7 and B.1.351 are 100 times more lethal than the original SARS-CoV-2 bearing 614D. Mice infected with B.1.1.7 and B.1.351 exhibited more severe lesions in internal organs than those infected with early SARS-CoV-2 strains bearing 614D or 614G. Infection of B.1.1.7 and B.1.351 also results in distinct tissue-specific cytokine signatures, significant D-dimer depositions in vital organs and less pulmonary hypoxia signaling before death as compared to the mice infected with early SARS-CoV-2 strains. However, K18-hACE2 mice with the pre-existing immunity from prior infection or immunization were resistant to the lethal reinfection of B.1.1.7 or B.1.351, despite having reduced neutralization titers against these VOC. Our study reveals distinguishing pathogenic patterns of B.1.1.7 and B.1.351 variants from those early SARS-CoV-2 strains in K18-hACE2 mice, which will help to inform potential medical interventions for combatting COVID-19.

immunology↗

bioRxiv2021

Functional and structural modifications of influenza antibodies during pregnancy

Pregnancy represents a unique tolerogenic immune state which may alter susceptibility to infection and vaccine-response. Here we characterized humoral immunity to seasonal influenza vaccine strains in pregnant and non-pregnant women. Pregnant women had reduced hemagglutinin subtype-1 (H1)-IgG, IgG1, and IgG2, hemagglutination inhibition and group 1 and 2 stem IgG. However, H1-specific avidity and Fc{gamma}R1 binding increased. Influenza-antibodies in pregnancy had distinct Fc and Fab glycans characterized by di-galactosylation and di-sialylation. In contrast, agalactosylation and bisection were prominent outside of pregnancy. H1-specific Fc-functionality was moderately reduced in pregnancy, although likely compensated by stronger binding to cognate antigen and FcR. Multivariate analysis revealed distinct populations characterized by Fc{gamma}R1 binding, H1-IgG levels, and glycosylation. Pooled sera from pregnant women exhibited longer retention in vivo. Our results demonstrate structural and functional modulation of humoral immunity during pregnancy in an antigen-specific manner towards reduced inflammation, increased retention in circulation, and efficient placental transport.

immunology↗

bioRxiv2020

Mapping the Antibody Repertoires in Ferrets with Repeated Influenza A/H3 Infections: Is Original Antigenic Sin Really "Sinful"?

The influenza-specific antibody repertoire is continuously reshaped by infection and vaccination. The host immune response to contemporary viruses can be redirected to preferentially boost antibodies specific for viruses encountered early in life, a phenomenon called original antigenic sin (OAS) that is suggested to be responsible for diminished vaccine effectiveness after repeated vaccination. In this study, we used a new computational tool called Neutralization Map to determine the hemagglutination inhibition profiles of individual antibodies within ferret antisera elicited by repeated influenza A/H3 infections. Our results suggest that repeated infections continuously reshape the ferret antibody repertoire, but that a broadly neutralizing antibody signature can nevertheless be induced irrespective of OAS. Overall, our study offers a new way to visualize how immune history shapes individual antibodies within a repertoire, which may help inform future vaccine design.

immunology↗